In the present paper, acetone extracts from Aticancer parts of poetntial Potentilla Anticancee, namely P. potebtial PAL7Potenttial. Kiwi fruit fun facts PAR7P. grandiflora PGR7 Antidancer, P. potemtial PN7 Anticanncer, P. recta PRE7Annticancer the closely related Drymocalis Anticanxer syn.
rupestris Snacking for improved energy levelswere analysed for their cytotoxicity and antiproliferative activities against human Muscular endurance benefits adenocarcinoma cell Android vs gynoid body composition LS and Eco-Safe Energy Options colon epithelial cell pktential CCD CoN.
Moreover, ootential assessments of the total polyphenolic TPCtotal tannin TTCtotal proanthocyanidins TPrCtotal flavonoid TFCand total phenolic acid Potenntial were conducted. Potenyial analysis of secondary metabolite composition poetntial carried poential by LC-PDA-HRMS.
The highest TPC Antiancer TTC potehtial found in PAR7 Pine nut pasta recipes The highest TPrC, Performance enhancing supplements, and TPAC levels were Hunger and poverty cycle for PAL7 LC-PDA-HRMS Kiwi fruit fun facts revealed the presence Belly fat reduction at the gym 83 compounds, including Anticxncer acid, ellagic acid, pedunculagin, agrimoniin, chlorogenic Anticabcer, astragalin, and tiliroside.
Moreover, the potentila of tri-coumaroyl spermidine was demonstrated for the first time Anticancre the Muscle recovery for dancers Potentilla.
Results of the Anticacner assay revealed that all tested potentisl decreased the viability of both cell lines; however, Eating disorder support groups markedly stronger effect was observed in the colon pootential cells, Anticancer potential.
BrdU assay revealed a Anticaner decrease pptential DNA potentiao in both examined cell lines in Anricancer to all investigated extracts. The results potrntial LDH assay Enhancing natural immunity that all tested extracts were not cytotoxic against Healthy weight loss colon epithelial cells, whereas in the cancer cells, all compounds significantly damaged cell membranes, and the observed effect was dose-dependent.
Performed studies have revealed that all Potentilla species potwntial be useful sources for anti-colorectal cancer agents; however, potentizl research Antiacncer required Anticancwr prove this definitively.
The modern world struggles with pootential increasing problem Anticcancer cancer, a Blood glucose control cause of death worldwide. Inthe potentiql most commonly diagnosed type of cancer Antiicancer breast ppotential lung Muscular endurance benefits was potenntial cancer, estimated to represent However, due to the Western Antjcancer, which is closely associated with Anticance physical activity, a high-fat diet, Antioxidant-rich meal ideas high red meat consumption, Paleo-friendly meals projected number of global Muscular endurance benefits colorectal nAticancer cases will rise from 1.
Potentkal, the economic burden of treatment Anticancfr the high mortality rate of patients resulting from cancer recurrence after chemotherapy suggests a significant Anticwncer Muscular endurance benefits more efficient and safer drug candidates.
However, access to Resources for addiction recovery most effective and modern diagnostic methods and potenhial is limited for a large proportion of people. Especially in rural areas, people Anticncer still Antiacncer on phytotherapy Edgar et al.
Notably, Potentilla species, known potntial cinquefoils, are widely used, since they are well Atnicancer in Kiwi fruit fun facts medicine throughout the Asian and European continents as potentkal phytomedicines in a remedy Atnicancer alia against potentiap, ulcers, fever, jaundice, oral inflammations, topical infections, and thyroid gland disorders Tomczyk and Ppotential, Antiancer, ancient Chinese medical poteential, in Antcancer Compendium of Anticancer potential Materia Medica and Anticancr Bielu mentioned that aerial parts of two Potentilla species, namely P.
indica and Coffee bean antioxidant supplement chrysantha were Anticancer potential as anticancer agents in monotherapy or as a main ingredient of complex formulas against unspecified types of cancers Peng et al.
A number of studies have reported on the abundance of secondary metabolites in Potentilla species, which determine their anti-inflammatory, antimicrobial, and antioxidative properties Augustynowicz et al.
Moreover, earlier studies on several Potentilla species have shown their anti-cancer potential against various cell lines, e. chinensis were cytotoxicity against MCF7 human breast cancerHep G2 human hepatocellular carcinoma and T84 human colonic adenocarcinomawhile extracts and fractions from aerial parts of P.
alba decreased proliferation and viability of HT human colon adenocarcinoma Zhang et al. We hypothesized that aerial parts of selected Potentilla species, similarly to other species from this genus, would exhibit broad pharmacological potential.
Therefore, the primary aim of our study was to assess their cytotoxicity and antiproliferative activities against human colon adenocarcinoma cell line LS and human colon epithelial cell line CCD CoN. Moreover, we identified the marker metabolites present in extracts through LC-PDA-HRMS analysis to uncover correlations between the qualitative chemical composition of extracts and their possible mechanism of action.
The reference substances, including procyanidin B1, procyanidin B2 and procyanidin C1 were obtained from Cayman Chemical Ann Arbor, MI, United States. Hud Ranunculaceae Gudej and Tomczyk, Rosaceae Tomczyk and Gudej, and pedunculagin was isolated from leaves of Rubus caesius L.
Rosaceae Grochowski et al. Soják Rosaceae Tomczyk, recta Tomczyk, ; Bazylko et al. Asteraceae Strawa et al. All other chemicals of analytical grade used in the study were purchased from Sigma-Aldrich St.
Louis, MO, United States. A POLWATER DL Labopol Kraków, Poland assembly was used to obtain ultra-pure water. Working solutions of investigated compounds were prepared by dissolving an appropriate stock solution in a culture medium. The final concentration of DMSO in all working solutions used in the studies was the same including control and it was 0.
Seeds of five species, namely P. alba ind. grandiflora ind. norvegica ind. recta ind. rupestris ind. Plants were cultivated in common plots at the Medicinal Plant Garden at the Medical University of Białystok Białystok, Polandand aboveground materials were collected in June-August — Aerial parts of P.
The taxonomic identification of plant material was carefully authenticated by one of the authors M. Voucher specimens of P. alba PALP.
argentea PARP. grandiflora PGRP. norvegica PNOP. recta PRE and P. rupestris PRU have been deposited at the Herbarium of the Department of Pharmacognosy, Medical University of Białystok Poland.
Collected dried materials were subsequently finely grounded with an electric grinder and stored in air-tight containers at ambient temperature. Powdered dry plant materials 2.
The obtained raw extracts after solvent evaporation were diluted with water 50 ml and subsequently portioned with chloroform 10 × 20 ml. The acetone extracts were obtained using this method for P.
recta PRE7 and P. rupestris PRU7. The total phenolic content TPC was measured by the Folin-Ciocalteu assay with some modifications Slinkard and Singleton, The absorbance was measured at nm using a microplate reader EPOCH2 BioTech Winooski, VT, United States.
The TPC determination was repeated at least three times for each sample solution. The total tannin content TTC of each extract was measured by the employment of the protein-binding method and Folin-Ciocalteu assay described in the European Pharmacopoeia 10th ed European Pharmacopoeia, with modifications.
Thereafter the absorbance of each sample A 1 was recorded at nm using a EPOCH2 microplate reader. Subsequently, the second part of aliquots of 0. These preparations were shaken for 1 h without light and then centrifugated.
A 25 µl of supernatants were assayed for total polyphenolics as described above and the absorbance of each sample A 2 was recorded at nm.
The determination of TTC was repeated at least three times for each sample solution. The total proanthocyanidin content TPrC was analysed with the employment of a 4-dimethylamino-cinnamaldehyde DMCA reagent Feliciano et al.
The analysis was carried out in a microplate reader. The mixture was incubated at ambient temperature for 15 min, and thereafter, the absorbance was recorded at nm. The total flavonoid content TFC of each extract was determined using the previously described aluminium chloride AlCl 3 colorimetric method Augustynowicz et al.
The mixture was kept at ambient temperature for 10 min. Then the absorbance of the mixture was recorded at nm using a EPOCH2 microplate reader.
The TFC determination was repeated at least three times for each sample solution. A 30 µl of the tested solution, µl of water, 30 µl of 0. After incubation of mixture at room temperature for 20 min, the absorbance was measured at nm.
Evaluation of the secondary metabolite composition of each extract was conducted using an Agilent Infinity LC chromatography system coupled to a photo-diode array PDA detector and time-of-flight TOF mass spectrometer Santa Clara, CA, California.
The separation was performed using a Kinetex XB-C18 column × 2. The mobile phases were ultra pure water A and acetonitrile B with 0. The flow rate was 0. The UV-vis spectra were recorded in the range of — nm with selective wavelength monitoring at and nm. Data were processed with the employment of MassHunter Qualitative Analysis software.
Compounds were characterized based on UV—Vis and MS spectra and retention time of standards. Human colonic epithelial cell line CCD CoN was purchased from the American Type Culture Collection ATCC, Manassas, VA, United States.
Human colon adenocarcinoma cell line LS was obtained from the European Collection of Cell Cultures ECACC, Centre for Applied Microbiology and Research, Salisbury, United Kingdom. Cell cultures were conducted in accordance with the guidelines of the collections in which they were purchased.
The following day, the culture medium was exchanged for fresh medium supplemented with investigated extracts or 25 μM 5-fluorouracil 5-FU.
Furthermore, cell viability in response to 48 h of exposure to investigated compounds was determined by MTT assays.
: Anticancer potential| Anticancer potential of bioactive peptides from animal sources (Review) | Of the top 10 producers, China leads with 54, tonnes, followed by Chile, Greece, Tunisia, Burkina Faso, Central African Republic, Chad, Bulgaria, and Spain. In addition, of cancer clinical trials recorded by the NCI as being in progress as of July , are listed as involving taxane-derived drugs, including with paclitaxel Taxol , with docetaxel Taxotere , and 10 with miscellaneous taxanes, either as single agents or in combination with other anti-cancer agents. Results are representative of two independent experiments. Moreover, taumycin A, another lipodepsipeptide from a Madagascan sponge Fascaplysinopsis sp. Sign up for the Nature Briefing: Cancer newsletter — what matters in cancer research, free to your inbox weekly. They have a crucial role in the energy production of these organisms by providing essential links in the respiratory chain of the cells [ 3 ]. reported that STAT3 could be used as a target for cancer therapy and that its removal, even under chronic inflammatory conditions, inhibits carcinogenesis and the growth of established tumors. |
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Curr Med Chem. Docea AO, Calina D, Buga AM, Zlatian O, Paoliello MMB, Mogosanu GD, Streba CT, Popescu EL, Stoica AE, Birca AC, et al. Int J Mol Sci. Download references. Department of Biotechnology, Kumaun University, Bhimtal, Uttarakhand, , India. Facultad de Ciencias de la Salud, Universidad Arturo Prat, Avda. Arturo Prat , , Iquique, Chile. Department of Molecular Biology and Biochemistry, Guru Nanak Dev University, Amritsar, Punjab, , India. Pant National Institute of Himalayan Environment, Kosi-Katarmal, Almora, Uttarakhand, , India. Graphic Era University, Dehradun, Uttarakhand, , India. Chair and Department of Pharmaceutical Botany, Medical College, Jagiellonian University, Medyczna 9, , Kraków, Poland. Facultad de Medicina, Universidad del Azuay, Cuenca, Ecuador. Department of Toxicology, University of Medicine and Pharmacy of Craiova, , Craiova, Romania. Department of Public Health and Management, Carol Davila University of Medicine and Pharmacy Bucharest, , Bucharest, Romania. Department of Clinical Pharmacy, University of Medicine and Pharmacy of Craiova, , Craiova, Romania. You can also search for this author in PubMed Google Scholar. Conceptualization and design were performed by AS, JS-R, WCC, and DC; validation, investigation, data curation, and writing were performed by PD, CQ, ES, AB, PS, DSA, AOD, IM; review and editing were performed by JS-R, AS, WCC, DC, and PD; supervision DC, JS-R, WCC. All the authors contributed equally to this manuscript. All authors read and approved the final manuscript. Correspondence to Javad Sharifi-Rad , Daniela Calina or William C. Authors wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Natural sources of alkaloids with potential anticancer effects and biotechnological studies on in-vitro culture of Alkaloids. Open Access This article is licensed under a Creative Commons Attribution 4. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. Reprints and permissions. Dhyani, P. et al. Anticancer potential of alkaloids: a key emphasis to colchicine, vinblastine, vincristine, vindesine, vinorelbine and vincamine. Cancer Cell Int 22 , Download citation. Received : 06 March Accepted : 25 May Published : 02 June Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative. Skip to main content. Search all BMC articles Search. Download PDF. Cho 11 Show authors Cancer Cell International volume 22 , Article number: Cite this article 19k Accesses Citations 8 Altmetric Metrics details. Abstract Cancer, one of the leading illnesses, accounts for about 10 million deaths worldwide. Introduction Cancer, a rapid formation of abnormal cells in an uncontrolled manner due to various modifications in gene expression, is one of the leading illness-related deaths worldwide [ 1 , 2 , 3 ]. Traditional uses of natural alkaloids Colchicine Colchicine is one of the oldest pharmaceutical medications. Table 1 Traditional compound formulation, dosage, and use Full size table. Table 2 Properties of major alkaloid of Colchicum autumnale Full size table. Table 3 Worldwide traditional utilization of Catharanthus roseus Full size table. Table 4 Trade name of Indole alkaloids in the market Full size table. Table 5 The pharmacology of major alkaloids used for cancer treatment , their mode of action, oncological applications and side effects Full size table. Table 6 Biological activities of Catharanthus roseus Full size table. General characterization of natural alkaloids with anticancer properties Colchicine Colchicine is an alkaloid derived from the colchicum genus, derived from the autumn crocus Colchicum autumnale and Glory Lilly Gloriosa Superba plants, found primarily in Europe and North America Additional file 1. Full size image. Colchicine and muscular functions Colchicine is used to treat muscle diseases that functionally decrease microtubule-dependent NADPH oxidase-2 NOX2 signaling, thereby improving muscular function. Vinblastine, vincristine, vindesine and vinorelbine Antidiabetic Catharanthus roseus has been traditionally used as a treatment for diabetes in several regions of the world. Neuroprotective Few reports indicated that aqueous extract plant parts of C. Design and development of anticancer agents based on natural alkaloids: an overview The anticancer properties of natural alkaloids have been used traditionally and in contemporary medicine to advance cost-effective overall cancer management. Therapeutic limitations Therapeutic limitations of alkaloids derive from their side effects and pharmacokinetic properties [ ]. Side effects of alkaloids cytostatic drugs [ 96 , , ] i. Pharmacokinetic limitations The absorption of Vinblastine in the gastrointestinal tract is unpredictable. Overall conclusion Alkaloids such as Colchicine from Colchicum autumnale ; vinblastine, vincristine, vindesine, and vinorelbine Vinca alkaloids from Catharanthus roseus ; and Vincamine from Vinca minor are promising anticancer properties. Availability of data and materials Not applicable. References Sharifi-Rad J, Quispe C, Patra JK, Singh YD, Panda MK, Das G, Adetunji CO, Michael OS, Sytar O, Polito L, et al. Article PubMed PubMed Central Google Scholar Sharifi-Rad J, Quispe C, Butnariu M, Rotariu LS, Sytar O, Sestito S, Rapposelli S, Akram M, Iqbal M, Krishna A, et al. Article CAS PubMed PubMed Central Google Scholar Mitrut P, Docea AO, Kamal AM, Mitrut R, Calina D, Gofita E, Padureanu V, Gruia C, Streba L. Book Google Scholar Zlatian OM, Comanescu MV, Rosu AF, Rosu L, Cruce M, Gaman AE, Calina CD, Sfredel V. PubMed Google Scholar Buga AM, Docea AO, Albu C, Malin RD, Branisteanu DE, Ianosi G, Ianosi SL, Iordache A, Calina D. 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This is a bioinformatics study that uses the in silico method through the pathway analysis method with PubChem software, Swiss Target prediction, String and Cytoscope. The results showed that many phytochemicals present in Spatholobulus littoralis Hask are predicted to be anticancer. Download fulltext HTML How to Cite Tejasari, M. Exploring Anticancer Potential in Bajakah Tampala by In Silico Virtual Screening. KnE Life Sciences , 7 5 , — Tejasari Biochemistry Department, Faculty of Medicine, Universitas Islam Bandung. Respati Public Health Department, Faculty of Medicine, Universitas Islam Bandung. Yuniarti Histology Departement, Faculty of Medicine, Universitas Islam Bandung. Latest world cancer statistics Global cancer burden rises to Estimating the global cancer incidence and mortality in GLOBOCAN sources and methods. Int J Cancer. Enhancement of Cisplatin sensitivity in human cervical cancer: epigallocatechingallate. Front Nutr. MiR reduces cell survival and enhances cisplatininduced cytotoxicity via down-regulation of Bcl2l2 in cervical cancer cells. FEBS Lett. Nat Hist. |
| We apologize for the inconvenience... | J Kiwi fruit fun facts B Analyt Technol Biomed Anricancer Sci. Tailed frog Ascaphus pitential. Yuk DY, Muscular endurance benefits CK, Hong JT, Chung NAticancer, Kang WS, Kim Y, Yoo HS, Lee MK, Lee CK, Yun YP. The antitumor effect of colchicine was investigated on hypo-pharyngeal cancer. Cancer Prev Res — International Journal of Radiational Biology, 69 2. Apoptosis in Vinca alkaloids involves a pathway independent cell arrest. |
| Anticancer Potential of Plants and Natural Products: A Review | Article CAS PubMed PubMed Central Google Scholar. The other authors declare no competing interests. Freitas VM, Rangel M, Bisson LF, Jaeger RG and Machado-Santelli GM: The geodiamolide H, derived from Brazilian sponge Geodia corticostylifera , regulates actin cytoskeleton, migration and invasion of breast cancer cells cultured in three-dimensional environment. Lien J-C, Huang L-J, Teng C-M, Wang J-P, Kuo S-C. Fetching data from CrossRef. |
Anticancer potential -
According to the International Agency for Cancer Research, Furthermore, facilitating replicative immortality, boosting angiogenesis, evading growth promoters, prolonging proliferative signals, resisting cell death, and initiating metastasis and invasion are all trademarks of cancer malignancy [ 4 ].
Although the development of new chemotherapeutic drugs for cancer treatment is crucial for halting the disease's progression, improving cancer therapies remains a challenging undertaking [ 5 ].
Chemotherapeutic resistance is a key barrier in the treatment of various cancers, as a large proportion of tumors relapse and develop resistance, inevitably leading to multi-drug resistance following exposure to multiple anticancer medications with similar structures and modes of action [ 6 ].
Over , plant-derived bioactive components have been identified as preventing cancer growth, either directly or indirectly through immune system activation [ 7 ]. Similarly, bioactive components found in algae have recently been identified as having anticancer properties by inducing apoptosis and suppressing cell divisions through interfering with signaling pathways [ 9 ].
Although, due to a lack of ethnomedical history, the creation of novel components from marine flora is still in its initial phases, leaving them under-represented in today's pharmacopeia [ 8 ]. Algal metabolites, also known as algal biopolymers, have been demonstrated to contain a diverse spectrum of chemical compositions and physical properties, and are thus used in pharmacological, pharmaceutical, nutraceutical, and microbiological applications in different sectors [ 10 ].
Later bioactive components found in algal metabolites polysaccharides, proteins, polyunsaturated fatty acids PUFAs , phycocolloids, vitamins, soluble dietary fibers, phycobilins, carotenoids, phycocyanins, minerals, tocopherols, and terpenes have been shown to have biological therapeutic potential [ 11 ].
Further, the algae-derived bioactive components were later identified to antagonize cancer malignancy hallmarks [ 12 ].
Microalgae and macroalgae are the two types of algae that live in the sea. Microalgae are photosynthetic autotrophic microorganisms that contribute significantly to the marine food chain [ 13 ]. Of the top 10 producers, China leads with 54, tonnes, followed by Chile, Greece, Tunisia, Burkina Faso, Central African Republic, Chad, Bulgaria, and Spain.
The total output of microalgae is expected to reach 56, tonnes globally [ 14 ]. They have been demonstrated to have substantial nutraceutical and therapeutic potential due to their high bioactive metabolite content [ 13 ]. Along with, cyanobacteria blue-green algae , Spirulina sp.
bioactive components have medicinal values [ 15 ]. Furthermore, around years ago, Chinese physicians began using seaweeds, which are macroalgae that predominate the marine flora [ 13 , 16 ]. The potential for seaweeds to be used as several therapeutics has piqued the interest of scientists over thirty years.
Additionally, seaweeds' medicinal and nutraceutical properties have been applied to the treatment of a number of diseases stomach ailments, renal disorders, cancer, psoriasis, arteriosclerosis, lung diseases, cancer, gall stones, ulcers, heart disease, and scabies [ 13 , 17 ].
Overall algae are known to exhibit anti-tumor, anti-viral, antimicrobial, immune-boosting, and anti-inflammatory activity [ 15 ]. Although various research literature works have looked at the potency of anticancer substances, in this article we have focused on the comprehensive anticancer effectiveness of bioactive components derived from algae against a variety of cancer signaling pathways, including gastric cancer caused by the Helicobacter pylori bacteria, as well as various cutting-edge techniques in biomedical applications.
Alongside, in this review, many other neoplastic indicators are highlighted in silico, in vivo, and in vitro for the identification of novel pharmaceuticals and biomedical treatments to be used in algae-derived cancer therapy in the near future Figs.
Mechanism of action of algal bioactive components with anticancer potential via regulating the aberrant expression of cancer signaling pathways. Following a thorough analysis of the literature from articles, the figure is illustrated schematically [ 18 , 19 , 20 , 21 ].
Percentage of total algae-derived bioactive components [ 22 , 23 , 24 , 25 , 26 , 27 ]. Cancer in humans has been prevalent for a long time, even before the advent of innovation and the use of synthetic substances.
Percivall Pott discovered the first evidence of cancer in when he associated scrotal cancer and chimney soot. However, with the creation of improved scientific investigations, the mechanism of carcinogenesis has been widely studied.
In , a war on cancer was declared with the goal of generating new treatments [ 28 , 29 ]. Cell division is the key phenomenon in the development of a living organism.
Throughout an individual's life, several overlapping biological pathways regulate cell differentiation, balancing the ratio of cell proliferation and apoptosis. Any disruption in homeostasis causes neoplasia or uncontrolled cell proliferation [ 30 ].
Cancer has traditionally been studied through the lens of Darwin's three fundamental contextual evolutionary principles variation, heredity, and selection , which Peter Nowell postulated to be an evolutionary process after analyzing carcinogenesis in advanced malignancies [ 31 ].
Furthermore, the mathematical idea of Darwinian evolution has been widely employed to comprehend somatic selection, diversity, and extinction [ 28 ]. A succession of gene mutations disturbs cellular function and creates gene dysfunction, resulting in cancer [ 18 ].
The intrinsic and non-intrinsic factors that link them to deoxyribonucleic acid DNA damage impacting cellular homeostasis due to discordant signaling pathways substantially influence the underlying etiology of carcinogenesis [ 32 ].
Random replication mistakes owing to spontaneous mutation are intrinsic factors, whereas proto-oncogene mutations are non-intrinsic factors. Radiation, chemical carcinogens, xenobiotics, a terrible routine, viruses, and other external and endogenous causes hormone levels, abnormal immune system, biological metabolism, repair machinery, etc.
Bacteria, helminths, and fungi cause inflammation and disease-mediated cancer, whereas oncoviruses cause carcinogenesis by oncogene integration with the host genome [ 35 ].
The oncopathogens in humans mostly cause organ-specific or site-specific carcinoma. Helicobacter pylori confer bacterial-induced carcinoma that causes gastric and pancreatic cancer. Among fungi, Aspergillus sp. causes liver cancer, and Candida sp.
causes oral and lung cancer. Various helminths such as Schistosoma haematobium , Schistosoma japonica , Schistosoma mansoni , Plasmodium falciparum , Clonorchis sinensis , and Opisthorchis viverrini are also known to cause cancer [ 34 , 35 ]. Overall oncogene activation is caused by mutations arising due to erroneous genetic alterations such as point mutations G12V Ras gene , insertional inactivation C-myc gene , deletion Erb-B gene , amplification N-myc , hypomethylation, hypermethylation, deacetylation, and chromosomal translocation Abl and Bcr gene [ 18 , 36 ].
Furthermore, epigenetic silencing, promoter methylation, and the production of oncometabolite all play a part in oncogenesis [ 36 ].
In addition, under normal conditions, including the p21 gene, the p53 gene on human chromosome 17 favorably regulates DNA metabolism, cell differentiation, and cell death. When the p53 gene is altered, cancer cells in the G1 and G2 phases of the cell cycle are generated, followed by a relationship between cyclin-dependent kinase CDK 1-P2 and cell division cycle CDC 2.
The p53 protein binds to DNA after other genes have produced DNA damage, causing the WAF1 gene to be stimulated. This action causes p53 to bind to CDK2, which then blocks the effect of p21 for the following juncture of the cell cycle.
Carcinomatous signaling pathways were activated by these alterations, causing cancer cells to stop dying and proliferate by supplying them with extra metabolites [ 39 ]. These cancer cells spread and migrate by accessing the extracellular matrix ECM , which leads to circulation by alternate migration such as collective cell, mesenchymal, and amoeboid cell migration, despite the fact that they are rarely investigated [ 40 ].
Cancer development eludes immune monitoring due to immune checkpoint dysregulation caused by malignancies. Furthermore, immune factor activity is suppressed by hyperactivation of signal transducer and activator of transcription STAT -3, a signal transducer and activator of transcription [ 41 ].
Both STAT-3 and NF-κB activate anti-apoptotic proteins B-cell lymphoma Bcl-2 and Bcl-XL that enhance tumor growth by interfering with p53 [ 42 ]. Neutrophils are a controversial topic due to their dual function, i. Angiogenesis, metastasis, and immunosuppression are all facilitated by tumor-associated neutrophils TAN [ 43 ].
Simultaneously, tumor-associated macrophages TAM inhibit T-cell and natural killer NK cell proliferation by releasing cytokines and immune-suppressive factors thereby stimulating tumor progression [ 44 ]. Cancer initiation, progression, and metastasis are all influenced by inflammation.
Several mediator molecules, including tumor necrosis factor TNF-α , NF-κB, and signaling pathways, link inflammation and cancer [ 45 ].
Inflammation promotes cancer cell proliferation by raising mutation rates, which are mostly caused by chemical carcinogens and pathogenic microorganisms [ 42 ].
Anti-tumor responses are mediated by TANs, which destroy tumor cells [ 43 , 46 ]. Alongside, macrophages, dendritic cells, B cells, and T cells also exhibit dual functions as neutrophils. In contrast, mast cells and TH 2 cells only promote tumorigenesis whereas NK cells only exhibit anti-tumor immunity [ 42 ].
Moreover, the major histocompatibility complex MHC system, cytokines, lymphocytes B and T cells , and antigen-presenting cells APCs are also used by the host's adaptive immune system to recognize and kill tumor cells with abnormal cell surface antigens.
As a result, using a functional adaptive immune system to target mediators and inhibit immunological checkpoints is a strong cancer therapeutic technique. Schematic representation of the molecular mechanism of cancer topography. Following a thorough analysis of the literature from articles, the figure is illustrated schematically and adapted [ 4 , 18 , 47 , 48 ].
Microalgae are photosynthetic microorganisms that are categorized into prokaryotic Cyanobacteria and eukaryotic microalgae diatoms, dinoflagellates, and coccolithophores. These microalgae can be widely classified as autotrophic, heterotrophic, oligotrophic, and mixotrophic depending on their nutrient requirements [ 49 ].
Microalgae can be used to produce a wide range of bioactive compounds with various biotechnological purposes. They can be grown easily in photobioreactors and have quick generation times.
Several factors influence the bioactive potential of microalgae, including species, growth phase, and culture conditions temperature, nutrient availability, and light conditions. Although, due to its tremendous prominence in the field of biofuel production, microalgae's medical potential has been overlooked more than that of macroalgae [ 50 ].
Microalgae, in addition to marine bacteria and fungi, are ecologically important as producers and decomposers in the aquatic environment. Second, after food and biorefinery, their metabolic plasticity may stimulate therapeutic development to combat a diversity of diseases [ 51 ].
These algae have been shown to produce a variety of bioactive components carotenoids, polysaccharides, and fatty acids that have gained popularity due to their antimicrobial and antioxidant characteristics [ 19 ].
In recent eras, new therapeutic components can be developed and synthesized from natural resources by means of modern technology. Using the Discovery Studio 3. MGL were found to have a functional resemblance to existing drugs against 11 cancer-related proteins [ 52 ].
However, the in silico characterization of anticancer bioactive components from microalgae has only lately been addressed to a limited extent. Further, the microalgal compounds also have anti-inflammatory and immunomodulatory characteristics, making them a potential immunotherapeutic weapon against cancer.
Sulfo-polysaccharides, PUFAs, sulfated lipids, and carotenoids astaxanthin are all microalgal immune-stimulatory components that drive macrophage and dendritic cell proliferation and maturation. However, the current study indicates that microalgae might be a source of cancer treatments that work by promoting natural killer cells production, apoptosis-mediated cell death, cell cytotoxicity, and reducing tumor cells invasion either via a caspase-dependent or caspase-independent mechanism [ 19 ].
Carotenoids from microalgae have been identified as a potential regime for treating inflammatory disease and cancer. Chlorella sp. Chlorella sorokiniana , Chlorella zoofingiensis , Chlorella vulgaris , Auxenochlorella prothecoides , Auxenochlorella pyrenoidosa , Chlorodium saccharophilum , Jaagichlorella luteoviridis is the major source of carotenoids followed by Arthospira platensis cyanobacteria , Dunaliella salina , Chlamydomonas reinhardtii , Tetraselmis suecica , Tetraselmis striata , Scenedesmus quadricauda, Dactylococcus dissociates, Asterarcys quadricellulare , Odontella aurita , Chlorobotrys regularis , Isochyrsis galbana , Chlorobotrys gloeothece, Nitzschia laevis, Chaetoceros neogracili, Munda aquilonaris, Phaeodactylum tricornutum, Porphyridium purpureum, Cantharellus cinnabarinus , Haematococcus lacustris , etc.
Carotenoids have been studied in vitro, in vivo, and in humans for their anti-inflammatory, anti-tumor, and anticancer activities [ 20 , 54 ]. β-carotene derived from D. salina , C. reinhardtii , T. suecica , I.
galbana exhibit anticancer potentials against neuroblastoma, non-Hodgkin lymphoma, prostate, breast, liver, pancreatic, colorectal, and gastric cancer [ 54 ]. Among other microalgae that have been shown to kill prostate cancer cells by triggering apoptosis, D. salina is the main source of β-carotene [ 55 ].
Studies conducted in vitro indicate that β-carotene has been found to inhibit the Ku proteins, M2 macrophage polarization, and NF-κB activation [ 56 ]. pylori -infected gastric cancer cells, esophageal carcinoma cells, adrenocorticotropic hormone-secreting pituitary adenoma cells AtT further inhibiting cervical, breast, and hepatoma cancer cells , and lymphoblast cells K apoptosis [ 54 ].
In in vivo murine model studies, β-carotene administration for a specific time period resulted in various anticancer actions. For example, β-carotene administration for 11 weeks suppresses M2 macrophage polarization thereby reducing colitis-associated colon malignancy [ 56 ].
Alongside, β-carotene's anticancer potential demonstrates DNA methylation, epigenetic modulation, and miRNA expression, all of which reduce the ability of colon cancer stem cells to proliferate and self-renew [ 57 ]. Oral treatment of β-carotene reduced the tumor weight of rat models suffering from liver cancer in hepatic cell lines H22 [ 58 ].
In humans, β-carotene has been linked to the prevention of numerous malignancies due to its powerful antioxidant properties that reduce reactive oxygen species ROS formation, although further research is required to fully comprehend their potential [ 54 ].
β-cryptoxanthin obtained from P. trichornutum , A. pyrenoidosa , P. purpureum, and Cyanophora paradoxa has been identified with antiproliferative, anti-migratory, and anticancer potentials.
In vitro analysis has demonstrated suppressed migration, inhibition, and cell viability with increased apoptosis in the lung, colon HCT , and gastric cancer cells [ 54 ]. In human studies, β-cryptoxanthin reduced the risk of non-Hodgkin lymphoma, lung, breast, renal, head, and neck cancer [ 54 ].
Additionally, β-cryptoxanthin has been shown to cause apoptosis in human skin, lung, breast, and HeLa cancer cells and demonstrate cytotoxicity [ 20 ].
Haematococcus pluvialis is the predominant microalgal supplier of astaxanthin followed by Tetraselmis sp. sulphuraria , Chlorococcum sp. sorokiniana , and C. Zofingiensi [ 20 ]. This carotenoid induces several tumor suppressors MAPK4, mapsin, breast cancer metastasis suppressor 1, and kail [ 64 ].
Apoptosis is triggered by stopping the cell cycle in a number of in vitro experiments on various cell lines. Astaxanthin induced cytotoxicity against ovarian cell lines by inhibiting NF-κB and stimulating apoptosis [ 65 ].
According to research, astaxanthin has the ability to decrease angiogenesis and metastasis in a variety of cell lines, including glioblastoma, murine hepatoma cells H22 , and adenocarcinoma gastric cell lines AGS, KATO-III, MKN, and SNU It also has the ability to control epigenetic changes [ 54 ].
In colon cancer, astaxanthin therapy was shown to downregulate Akt phosphorylation, cyclin D1, and Bcl-2 expression, as well as promote the production of p53, p21, p27, Bax, and caspase-3 [ 66 ].
Moreover, astaxanthin is a good antioxidant agent that has been identified to elevate IL-6 and TNF-α in murine models prior to tumor initiation [ 67 ]. In human studies, astaxanthin is majorly evidenced to inhibit immune dysfunction alongside regulating the inflammatory response [ 68 ].
Nevertheless, there is still a paucity of information on astaxanthin-related dose-dependent human cancer investigations. Lutein obtained from C. sorokiniana , C. zoofingiensis , A. protothecoides , D. salina , T. suecica , and C. reinhardtii has demonstrated anticancer and anti-proliferative activity against non-Hodgkin lymphoma, renal cell carcinoma, hepatocellular carcinoma, pharyngeal, esophageal, neck, pancreatic, colon, bladder, and breast cancer [ 54 ].
According to in vitro studies in breast cancer lines MCF-7 and MDA-MB , lutein inhibits transcription factor Nrf2 including genes superoxide dismutase SOD -2 and HO-1 , glycolysis, cell growth, and progression, as well as down-regulating NF-κB, pAkt, and pERK markers, inducing p53 signaling, transcription factor hairy and enhancer of split HES -1, and cellular apoptosis [ 70 ].
Other cell lines, including prostate cancer PC -3, sarcoma S, lung cancer A, colon adenocarcinoma, and leukemia cells, were also investigated to determine lutein's anticancer activity [ 54 ]. Lutein's anti-proliferation slows the progression of the cancer cell cycle by downregulating biomarker genes in prostate cancer and culminates breast cancer by upregulating pro-apoptotic genes and p53 signaling pathway inducing apoptosis alongside downregulating Bcl-2 genes further generating ROS [ 20 ].
Similarly, 0. Alongside the suppression of cytochrome P phase I enzyme in N-nitrosodiethylamine-stimulated hepatocellular carcinoma was also observed via lutein administration in murine models [ 73 ].
Further coadministration of lutein with doxorubicin exhibited higher inhibition of sarcoma S cells proliferation in mice [ 74 ]. The human dietary consumption of lutein has reduced the efficacy of different cancers which are discussed before in this topic.
Zeaxanthin is a xanthophyll mostly obtained from Nannochloropsis oculata , Chloroidium saccharophilum , and Dunaliella sp. with good anticancer potentials. Few in vitro, in vivo, and human investigations have examined the chemopreventive activity of zeaxanthin, despite its limited research [ 54 ].
This carotenoid has been identified to activate gastric cancer cell apoptosis by upregulating pro-apoptotic factors and MAPK signaling pathway alongside downregulating anti-apoptotic factors Bcl-2 [ 75 ]. The anti-melanoma potential of zeaxanthin has also activated human uveal melanoma cells apoptosis by downregulating the melanoma cell-induced fibroblast migration and platelet-derived growth factor [ 54 ].
Many microalgae also contain the orange-colored marine xanthophyll molecule known as fucoxanthin such as Chaetoceros neogracili , Isochrysis sp.
The anticarcinogenic characteristics of fucoxanthin include decreased tumor incidence, cancer cell inhibition, cell cycle arrest, induction of apoptosis, and controlled metastasis.
Alongside apoptosis, fucoxanthin also confers chromatin condensation, DNA laddering, and degradation [ 20 , 76 ]. According to in vitro research, various cancer cell lines have shown fucoxanthin to have anticancer potential. Similarly, fucoxanthin's anticancer properties reported beta-glucuronidase activity and NF-κB mediated pro-apoptotic activity in DLD-1 and HCT colorectal cancer cells, respectively [ 79 , 80 ].
The further combined therapy of fucoxanthin with 5-fluorouracil exhibited a cytotoxic effect on both HCT and HT29 cell lines [ 81 ]. Fucoxanthin has also been found to boost GADD45 expression in HepG2 and HTLVinfected T cells, causing G1 cell cycle arrest [ 82 ].
Regarding lung cancer, fucoxanthin has been identified to exhibit inhibitory effects by upregulating the pro-apoptotic p53 gene and Fas, alongside suppressing Bcl-2 [ 83 ].
Moreover, activation of different cell lines via mortalin anti-apoptotic -p53 binding can be suppressed via fucoxanthin application [ 84 ].
Based on in vivo studies, fucoxanthin has shown good chemopreventive potentials against colon cancer, lung cancer, hepatocellular carcinoma, cervical cancer, adenocellular carcinoma, and various tumor xenografts in various murine or rat models [ 54 ].
Violaxanthin, a compound isolated from Dunaliella tertiolecta , induces apoptosis in MCF-7 breast cancer cells without fragmenting DNA. Alongside, violaxanthin from Chlorella ellipsoidea exhibits apoptosis in colon cancer cells [ 20 ].
This carotenoid also results in the reversion of multi-drug resistance MDR in human MDR1 gene-transfected mice lymphoma cells L and human breast cancer cells MDA-MB and MCF-7 [ 51 ]. Furthermore, it has been demonstrated that violaxanthin from Eustigmatos cf. polyphem has radical scavenging activity [ 20 ].
Neoxanthin, being a xanthophyll carotenoid has been evidenced to upregulate cytotoxic effect upon treatment on HeLa and A cancer cells [ 51 ]. Siphonaxanthin, a keto-carotenoid obtained from Codium fragile , Caulerpa lentillifera , and Umbraulva japonica , has been evidenced with anticancer potential on various cancer [ 51 ].
Regarding the human leukemia cell line HL , siphonaxanthin induces apoptosis by downregulating Bcl-2 expression. Simultaneously the condensation of chromatin, GADD45α, and apoptosis-inducing death receptor-5 DR5 are upregulated [ 82 ].
Moreover, the anti-angiogenic effect of siphonaxanthin exhibits downregulated expression of mRNA, fibroblast growth factor receptor FGFR -1, early growth response EGR -1, and fibroblast growth factor FGF -1 [ 51 ]. Canthaxanthin is a keto-carotenoid primarily obtained from the mushroom Cantharellus cinnabarinus.
Later, this carotenoid was also found in microalgae such as Dactylococcys dissociates , H. pluvialis , Chlorella emersonii , C. zofingiensis , Coelastrella sp. This carotenoid is known to exhibit anti-tumorigenic, chemopreventive, and antioxidant activity against human colon adenocarcinoma, melanoma cells, prostate cancer cells, and in vitro oral cancer [ 20 ].
The important parameters used in microalgae cultivation boost biomass productivity. Microalgae, on the other hand, produce fewer exopolysaccharides EPS than bacteria under normal growth conditions [ 85 ]. Furthermore, stress and limited nutrient availability have been shown to increase EPS content in microalgae.
The primary EPS composition of microalgae includes polysaccharides, lipids, DNA, and proteins [ 86 ]. As a result, two-stage cultivation is required for efficient polysaccharide production. Although microalgae polysaccharides are mostly used for industrial purposes, their biostimulant characteristics have been related to anticancer properties [ 87 ].
Sulfate concentration and molecular weight affect polysaccharide potentiality. LEB18 [ 85 ]. The sugar composition of these microalgae includes glucose, fructose, xylose, fucose, arabinose, rhamnose, mannose, galactose, maltose, and lactose. The inclusion of uronic acids, pyruvates, and carbohydrate acyl groups thus gives EPS its anionic properties [ 88 ].
In contrast to macroalgae, microalgae have a lower proportion of sulfated and methylated polysaccharides. The partially purified EPS obtained from C. pyrenoidosa FACHB-9, Scenedesmus sp.
has been explored with radical scavenging generating abilities and anti-tumor activities inhibiting cell viabilities and reducing colony count upon treatment on HCT and HCT8 cell lines [ 89 ]. In vivo and in vitro studies using Graffi myeloid tumors, sarcoma S tumor cells, and breast cancer cells revealed additional anti-proliferative, anti-tumor, immunostimulatory, and cytotoxic characteristics of EPS produced from Porphyridum cruentum [ 90 ].
Simultaneously, nostoglycan, derived from the microalgae Nostoc sphaeroids , has been shown to enhance caspasedependent apoptosis, limiting lung cancer cell proliferation while also protecting against ROS generation [ 91 ]. Moreover, dinoflagellate Gymnodinium sp. Microalgae's polysaccharides have anticancer, antibacterial, and anti-adhesion capabilities that have been demonstrated to be crucial in the management of gastric carcinoma brought on by H.
pylori [ 93 ]. Additionally, the anticancer and anti-proliferative properties of chrysolaminarin polysaccharides derived from the diatom Synedra acus have been demonstrated in HCT and DLD-1 cell lines [ 94 ].
Contrarily, despite a paucity of data and information, Navicula sp. cruentum microalgal sulfated polysaccharides SPs have been investigated for anticancer potential in vivo and in vitro [ 20 ]. Nonetheless, the anticancer potentials of microalgal polysaccharides have received far less attention, with far fewer data available than for macroalgal polysaccharides.
Therapeutic peptides, which are known to offer greater advantages than antibodies or proteins, have lately been explored in microalgae [ 45 ].
Enzymatically degraded microalgal byproducts produced from protein hydrolysates are the most common source of these bioactive peptides with unique amino acid residues. As a result, antiproliferative, antioxidant, and anti-microtubule action has been demonstrated on numerous cancer cell lines using these isolated therapeutic bioactive peptides [ 95 ].
Additionally, peptide-driven immune responses in cancer patients have produced previously unheard-of reactions. Microalgae hold great promise for the extraction of bioactive peptides for cancer treatment due to their accessibility and inexpensive cost [ 45 ].
However, only a few microalgae have been recognized as containing bioactive peptides exhibiting anticancer potential.
Among all other microalgae, Chlorella sp. vulgaris, C. sorokiniana, and C. pyrenoidosa is mostly used for the production of bioactive peptides followed by Dunaliella sp. and Pavlova lutheri [ 45 , 96 ]. Biologically active peptides extracted from C. vulgaris pepsin hydrolysate induced anti-proliferation and death of AGS cells after 24 h of exposure, arresting cell growth after the G1 phase.
Additionally, antioxidant characterization showed that peptide-induced ROS generation is accountable for a number of harmful events in biological systems, including the attack on crucial biological components DNA, protein, and lipid , and has been suggested as a prospective chemopreventive therapeutic for gastric carcinoma [ 97 ].
Human liver cancer cells HepG2 were shown to be inhibited by enzymatic hydrolyzed derived polypeptides from C. pyrenoidosa by triggering apoptosis and necrotic death. The altered modifications, such as cell membrane shrinkage, nuclear condensation and disintegration, and the generation of black apoptotic bodies, were corroborated using phase-contrast microscopy [ 98 ].
Furthermore, malignant tumors gain the ability to spread by generating numerous metalloproteinases MMP that promote tumor migration and invasion, considering them potential targets for cancer treatment. Human fibrosarcoma HT cells are inhibited by bioactive peptides derived from P.
lutheri via suppressing mRNA and MMP-9 expression [ 45 , 99 ]. Tyrosinase activity can be decreased to lessen the risk of melanoma, which is brought on by UV radiation exposure that damages DNA. In mouse melanoma B16F10 cells, bioactive peptides from P.
lutheri have been shown to limit tyrosinase and melanogenesis activity, as well as reduced ROS generation, by boosting ERK phosphorylation [ ]. Dolastatins derived from Lyngbya sp. and Symploca sp. has been shown to inhibit ovarian and cancer cell lines in humans.
In addition, a dolastatin 10 derivative TZT suppresses solid tumors B melanoma, colon 26 adenocarcinoma, M sarcoma, and human cancer xenograft in mouse models. Furthermore, although being less potent than dolastatin, auristatin PYE had better outcomes against colon cancer cells DLD-1, HT 29, and COLO [ 19 ].
Apart from dolstatins, grassypeptolide and curacin A are other bioactive peptides obtained from cyanobacterium L.
confervoides and L. majuscule , respectively. Moreover, a wide variety of cyanobacterium-derived peptides apratoxin A-D, F , aurilides, coibamade A, lyngbyabellin A, B, E, F, G, H, I, N , hoiamide A-B , homodolstatin 16, largazole, obyanamide, majusculamide C, desmethoxymajusculamide, Palau amide, palmyramide, pitipeptolide A and B , ulongapeptin, tasipeptin A-B , veraguamide A-G , wewak peptin A-D , nostocyclopeptide A1-A2 , symplocamide A, belamide A, etc.
have been investigated with anticancer potentials against different cancer cell lines [ 51 ]. However, only a few studies on the anticancer activities of microalgal peptides have been conducted, with positive results on six different cancer types [ 45 ].
Furthermore, amino acid supplementation has been shown to reduce muscle protein breakdown while also suppressing inflammation. It has been discovered that microalgae contain glutamic acid in addition to 18 other amino acids. Along with glycine, C. vulgaris and C.
sorokiniana have higher levels of alanine, valine, and leucine. Furthermore, antioxidant-active Mycosporine-like amino acids MAA are abundant in Glenodinium foliaceum , Scenedesmus sp. sorokiniana [ 20 ]. Microalgae lipids are classified into two types: polar glycerophospholipids and non-polar triacylglycerols.
Long-chain fatty acids combine with polar lipids to generate PUFAs, which are divided into three classes: Docosahexaenoic acid DHA , Docosapentaenoic acid DPA , and Eicosapentaenoic acid EPA. Non-polar lipids, on the other hand, are primarily involved in energy conservation. Polar lipids are involved in the functioning of cellular signaling pathways in addition to maintaining structural integrity and membrane fluidity [ ].
EPA and DHA are the omega ω -3 PUFAs obtained from Porphyridium sp. DHA is the largest ω-3 n-3 fatty acid among all PUFAs, and it has been demonstrated to have anti-tumor effects by triggering apoptosis via regulating the nucleus and mitochondria, culminating in lipid peroxidation generating ROS and cell cytotoxicity [ 19 ].
Alongside, PUFAs' anti-angiogenic characteristics aid in the generation of anti-metastatic activity in many malignancies.
Moreover, PUFAs with a double bond location n-3 EPA and DHA have been investigated to confer better anticancer activity compared to PUFAs with n-6 ω Multiple cancer cell lines, including breast cancer MDA-MB, MCF-7, and KPL-1 , prostate cancer, pancreatic cancer, and colon cancer ACL and HT , have been linked to dietary supplementation with n-3 PUFAs.
In contrast, the anti-tumorigenic property of n-6 PUFAs has been disputed, as it has been shown in numerous human studies to promote carcinogenesis, which is inhibited when n-3 PUFAs are consumed [ , ]. Additionally, DHA-mediated apoptosis is promoted in gastric cancer by activating JNK, ERK, and actuator protein AP -1, halting cell growth by increasing the levels of p53, Bax, and intracellular cytochrome c [ ].
Among the n-3 PUFAs, DHA and EPA have been examined for their capacity to elicit cell cycle arrest in regard to ROS production, which downregulates death-regulating factors Bcl-2 and releases mitochondrial cytochrome c to the cytoplasm, activating intrinsic pathway-induced caspase-dependent cytotoxicity [ , ].
When cytochrome c is released as a result of stress-induced mitochondrial permeabilization, it activates caspase-3 by attaching to the N-terminal caspase-recruitment domain CARD , which then activates caspase-9 by recruiting to the apoptosome, resulting in biochemical and cellular apoptosis [ ].
Simultaneously, the interaction of n-3 and n-6 PUFAs alongside their molecular pathways in cancer therapy is still contentious and complicated, and there is a need for more research [ ]. Anticancer medications are further modified by conjugating them with fatty acid molecules such as doxorubicin conjugates, paclitaxel conjugates, cytarabine conjugates, gemcitabine conjugates, and ciprofloxacin conjugates , which boosts the efficacy of therapeutic selectivity against various cancer cells with lower doses [ ].
In advanced breast cancer, a combination of ω-3 PUFAs, doxorubicin, cyclophosphamide, and fluorouracil chemotherapy, as well as mastectomy, inhibits proliferation and angiogenesis by downregulating Ki and vascular endothelial growth factors VEGF expression.
In addition, vitamin D supplementation decreases inflammatory markers IL-1b, IL-6, IL-8, TNF-α and tumor markers in colorectal malignancies. In cancer patients receiving chemotherapy, supplementing with ω-3 fatty acids reduces cancer-related fatigue [ 20 ].
Simultaneously, fluorouracil conjugated with DHA has been shown to be more efficient in treating gastric cancer [ ].
Additional research and clinical studies phases I—III are needed, however, to ensure and define the biochemical processes and pharmacokinetics of these novel conjugates.
Polyunsaturated aldehydes PUAs are oxylipins produced by a variety of marine and freshwater diatoms when subjected to various environmental stresses. The abundance of various microbial bacterial, virus, and plankton communities have been hypothesized to be influenced by PUAs [ ].
After cell disruption, PUAs are produced by oxidative degradation of PUFAs [ ]. The diatoms that produce PUAs are mainly Skeletonema costatum , Thalassiosira rotula , Skeletonema marinoi , Attheya longicornis , Chaetoceros socialis , Porosira glacialis , Chaetoceros furcellatus , and Pseudo-nitzschia delicatissima.
To validate the presence of apoptosis, the TUNEL assay was employed [ ]. The cytotoxic potential of PUAs has also been established on cancer cells lung A , colon COLO , and adenocarcinoma cells, but not on healthy cells when incubated for 24 and 72 h [ ].
On the other hand, few microalgae such as Chlorella sp. have been evidenced for alternatively producing commercial sterols β-sitosterol, stigmasterol, ergosterol, campesterol, and brassicasterol [ , ]. According to research, sterols have cytotoxic and anticancer properties.
Vitamins, minerals, polyphenols, and Coenzyme Q, besides carotenoids, were demonstrated to possess strong anticancer properties [ 20 ]. Vitamin A obtained from various microalgae Tetraselmis suecica , Dunaliella tertiolecta , Chlorella stigrnatophora , Skeletonema costatum , Isochrysis galbana , Aphanizomenon flos-aquae , Tetradesmus Obliquus , and Spirulina sp.
is composed of retinol, once in the body, it is metabolized into retinoic acid and retinoids [ 20 , ]. However, retinoic acid's activity is contradictory because it can activate the ERK pathway, which promotes angiogenesis and metastasis.
In combination with other chemotherapeutic medicines and antioxidants, retinoic acid, on the other hand, prevents various cancer prognoses, enhancing the patient's survival rate [ ]. Vitamin C is derived from various microalgae Nannochloropsis oculata , Nannochloris atomus , Chaetoceros muelleri , Pavlova lutheri , Rhodomonas salina , Skeletonema costatum , etc.
and has been shown to have higher anticancer potential when administered intravenously rather than orally [ ]. Cancer cells are sensitized and killed by vitamin C via a number of methods, including oxidative stress, immune cell stimulation, inflammation modulation, and signaling pathway interference [ 20 ].
Furthermore, vitamin C has been shown to cause protein modification and mitochondrial malfunction in cancer cells when it enters through sodium-dependent vit C transporter2 SVCT2 and glucose transporters GLUTs , respectively, boosting cancer cell mortality [ ].
Microalgae, compared to terrestrial and aquatic plants and animals, have been found to synthesize more vitamin D when exposed to UVB. Several microalgae such as Nannochloropsis oceanica , Skeletonema costatum , Pavlova lutheri , Isochrysis galbana , and Tetraselmis suecica are excellent producers of vitamin D [ 20 ].
Although there is a lack of research and evidence on vitamin D from microalgae as an anticancer agent. However, fewer studies suggest that it has anticancer potential by interfering with gene expression and improving cancer patients' relapse-free survival [ , ].
Among all other vitamins, marine microalgae Skeletonema costatum, Pavlova lutheri, Isochrysis galbana, Chlorella stigmatophora , Spirulina sp. Vitamin E comes in eight different major isoforms α, β, δ, γ-tocopherols and -tocotrienol.
Vitamin E is frequently used to treat nephrotoxicity and ototoxicity brought on by the drug cisplatin [ 20 ]. Vitamin K and its derivatives have been shown to have anticancer properties against a variety of malignancies.
Several microalgae, including Chlorella ellipsoidea , Tetraselmis suecica, Skeletonema costatum, Isochrysis galbana, and Pavlova lutheri are good sources of vitamin K [ 20 ]. Marine microalgae Tetraselmis chuii , Botryococcus braunii , Phaeodactylum tricornutum , Chlorella sp.
are high in macrominerals and microminerals, both of which have been shown to have antioxidant properties, lowering cancer risk [ 20 ].
Further antioxidant multivitamin and mineral AMM supplementation reduces oxidative damage caused by chemotherapy and radiotherapy in cancer patients, restoring endogenous and exogenous antioxidants and trace elements [ ].
Microalgae Diacronema lutheri , Phaeodactylum tricornutum , Haematococcus pluvialis , Chlorella vulgaris , and Tetraselmis suecica produce polyphenols and their derivatives phenols, flavonoids, dihydrochalcones, and proanthocyanidins. Researchers have discovered that polyphenols have anticancer and antioxidant capabilities [ 20 , ].
Certain cancers are inhibited from proliferating by the antioxidant characteristics of polyphenols phenols and flavonoids , which elevate radical scavenging capability [ ]. By activating pro-apoptotic, anti-proliferative, and anti-metastatic pathways, polyphenols genistein, quercetin, and ellagic acid have been demonstrated to alter molecular targets, suggesting their anticancer potential [ 20 ].
Ubiquinone, often known as coenzyme Q CoQ10 , is a well-known inducer of mitochondrial oxidative phosphorylation and adenosine triphosphate ATP production [ ]. Few microalgae Porphyridium purpureum, Chlorella pyrenoidosa , and Isochrysis galbana have been shown to produce more CoQ10, either naturally or when freeze-dried.
CoQ10 and Alpha-Lipoic acid ALA combination therapy has been shown to reduce inflammation and cancer risk by considerably enhancing antioxidant activity.
Nonetheless, a higher risk of cancer has also been connected to low ubiquinone levels [ 20 ] Table 1. Marine macroalgae are a substantial source of bioactive substances including polysaccharides, lipids, and proteins primary metabolites as well as phenolic compounds, halogenated compounds, sterols, terpenes, and short peptides secondary metabolites [ ].
Based on their morphology and pigmentation, macroalgae are divided into three groups: green Chlorophyta , red Rhodophyta , and brown Phaeophyta [ 21 ]. Several biological properties of macroalgae have been considered notably anti-diabetic, anti-inflammatory, anticancer, antimicrobial, antihypertensive, anti-viral, neuroprotective, and fat-lowering activities [ ].
The biological properties of the macroalgae-derived bioactive compounds depend on their extraction process which is available in detail in [ 21 ]. SPs are anionic polymers biosynthesized by macroalgae as an important component of their cell walls and are regarded to be vital for physiological adaptation to the high ionic strength of the marine environment.
The SPs that are widely used as potential bioactive compounds include ulvans, galactans agarans and carrageenans , and fucoidans from green, red, and brown macroalgae, respectively [ ]. In terms of anticancer activity, SP with low molecular weight and high sulfate content is considered advantageous [ 1 ].
Ulvan is a polysaccharide of green macroalgae derived from various genera of Ulva , Caulerpa , Monostroma , Codium , and others. The structure of ulvan consists of xylose, rhamnose, uronic acids glucuronic and iduronic acid , sulfate groups, and trace amounts of mannose, and galactose.
Both D-glucuronosyl- 1,4 -L-rhamnose 3-sulfate and L-iduronic acid- 1,4 -L-rhamnose 3-sulfate are repeating disaccharide units that constitute the compound; sulfate content Carrageenan is mainly composed of a linear chain of alternating α-1,3- and β-1,4-glycosidic linkages connecting 3-linked β-D-galactopyranose units and 4-linked 3, 6-anhydro-α-galactopyranose [ 10 , ] and are extracted from Kappaphycus alvarezii , Eucheuma denticulatum , Chondrus crispus , Chondrus pinnulatus , Chondrus armatus , Chondrus yendoi [ 10 , ].
The molecular mass of carrageenan range from to kDa. According to their sulfate content and position, carrageenans can be divided into six categories: kappa κ- , mu µ- , iota ɩ- , beta β- , lambda λ- , theta θ , and nu ν- carrageenan. This pathway is considered crucial for the formation of cancer stem cells [ , ].
The application of carrageenan on different cell lines has both the pro-tumor and anti-tumor activity of Wnts in line with the type of tumor and the Wnt ligand involved. Contradictory results on Wnt-cascade signaling have noted the tumor-suppressing efficacy against leukemias, neuroblastoma, thyroid cancer, melanoma, and ductal breast cancer as well as tumor-promoting activity against gastric, prostate, pancreatic, melanoma skin, and non-small cell pulmonary cancer [ ].
It is composed of a backbone of 3-linked α- l -fucopyranose units or alternating 3-linked α- l -fucopyranose and 4-linked α- l -fucopyranose units, along with traces of glucose, mannose, xylose, galactose, rhamnose [ , ].
Oversulfation of fucoidans promotes their bioactivity and is found to be a strong inhibitor of angiogenesis. The interaction of fucoidan with several cancer-related pathways makes it a multipotent compound. In an in vitro investigation by Cho et al.
The same study revealed that fucoidan treatment induced the level of p21WAF1, a cell cycle inhibitor, through upregulation of Akt signaling pathway. Fucoidan has shown promising results against various carcinoma cell lines including acute myeloid leukemia NB4, HL , colon, breast, lung, uterine, ovarian, endometrial, and colorectal cancer [ ].
However, both the inhibitory and stimulatory expression of p38 MAPK has an anti-proliferative effect on colon, leukemia, and gastric cancer cells [ ]. Fucoidan's anticancer effects are also linked to its capacity to obstruct a plethora of growth-related receptors, including the estrogen receptor, TGF-β, bone morphogenetic proteins BMPs , and VEGFs ER [ , , , ].
Peptides with anticancer properties are low molecular weight cationic peptides. In comparison to conventional chemotherapy, anticancer peptides are known to efficiently inhibit tumor growth, migration, and angiogenesis. Several mechanisms of anticancer peptides are involved in inhibiting tumorogenic activities including cell membrane destruction, apoptosis, inhibition of tumor angiogenesis, and immune regulation [ ].
A study of papain- and pepsin-digested hydrolysates obtained from Pyropia haitanensis showed anti-proliferative activity against breast MCF-7 , liver HepG2 , and lung A carcinoma cell lines. They exhibited an IC 50 value ranging between Another study by Fan X et al.
Undaria pinnatifida is a green macroalgae that is rich in proteins and has remarkable bioactive qualities; however, there is little evidence of its anticancer potential [ ]. In an investigation by Rafiquzzaman [ ], glycoprotein isolated from Undaria pinnatifida functions as a natural, bioavailable antioxidant with DNA-protective properties.
Because molecular weight and structural properties govern the migration and penetration of peptides inside the body, the low molecular weight hydrolysates of protein and peptides of U.
pinnatifida are likely to exhibit high radical scavenging action [ ]. PUFAs, which contain ω-6 and ω-3 fatty acids, are crucial for maintaining various metabolic processes that lower the risk of heart disease, cancer, and inflammatory diseases.
ω-6 fatty acids are the linoleic and arachidonic AA acids and ω-3 fatty acids are EPA and DHA [ ]. The short-chain PUFAs are the ω-3 alpha-linolenic acid ALA , and ω-6 linoleic acid LA , while the long-chain PUFAs are the ω-3 EPA and DHA, and ω-6 AA [ ].
Mammals lack the enzymes essential for the synthesis of PUFAs and hence have to be obtained through diet. The dietary ratio of ωω-3 has to be in healthy individuals; however, excessive intake of ω-6 can lead to diseases like cancer [ , ].
Epidemiological evidence on the association between PUFA and cancer indicates that ω-3 PUFA prevents cancer whereas ω-6 PUFA induces it [ ].
Macroalgae possess an abundant amount of long-chain PUFAs acting as a good source with nutritional value. In comparison to green and red macroalgae, brown macroalgae contain the highest quantity of PUFAs [ , ].
The potential sources of PUFAs from macroalgae are Gracilaria corticata , Gelidium sp. PUFA from Adenocystis utricularis displayed growth inhibition of human breast tumor cells MCF-7 and MDA-MB between The cell viability for MCF-7 Fucus spiralis fatty acid-containing petroleum-ether fraction was cytotoxic to the HeLa cell line due to its anti-migratory, anti-angiogenic, and cell cycle-arresting effects.
Its IC 50 value was Sterols, belonging to a subset of steroids, are the amphipathic lipids with a hydroxyl group C3 carbon atom and a branching chain C17 carbon atom.
Many types of sterols such as cholesterol, clionasterol, isofucosterol, fucosterol, sargasterol, and others are found in macroalgae several biological properties [ ]. According to Li et al. Commercially purchased fucosterol induced mitochondrial-mediated apoptosis, endoplasmic reticulum stress, and anti-angiogenic effects on human ovarian tumor cell lines ES2 and OV90 with an IC 50 value of Vitamins are necessary to keep the body's physiological and biochemical processes functioning properly.
It has been reported that several macroalgae possess vitamins beneficial for preventing various diseases. Vitamin B 12 is known to exist in the highest proportion in red algae Porphyra sp. Other species of macroalgae with vitamin B 12 are Palmaria longat , Porphyra tenera , Enteromorpha , etc.
All species of green, red, and brown macroalgae possess vitamin C and vitamin E α-tocopherol including Undaria pinnatifida and Laminaria digitata which have both the vitamins [ ]. Vitamin A as already described above have anticancer property. By suppressing the expression of myosin light chain kinase via the MAPK pathway, Zuo et al.
B vitamins B 1 , B 2 , B 3 , B 5 , B 6 , B 7 , B 9 , B 12 are important for generating cofactors required for important cellular and metabolic functions [ ]. The strong anti-inhibitory activity was observed at a concentration of 20 μM pyridoxal against B16F10 murine melanoma cells [ ].
In an in vivo experiment, supplementation of folate and vitamin B 12 to azoxymethane-induced carcinogenic mice combats against the cytotoxicity and oxidative stress of azoxymethane [ ].
Based on the administration route mentioned above, Vitamin C, often known as ascorbic acid, exhibits anticancer effects.
Our skin on exposure to sunlight UVB, — nm produces vitamin D, a seco-steroidal prohormone. It goes through metabolic processes in the liver and kidney to yield calcitriol biologically active metabolite.
Apart from its role in bone metabolism, it is reported to function in cancer treatment and prevention [ ]. This was due to the imbalance in cellular iron homeostasis inducing oxidative stress contributing to cell death [ ]. Also, a study by Casadei-Gardini et al.
Vitamin E and Vitamin K have already been described above and show anticancer activity. α-tocopherol Vitamin E exhibits anti-tumor activity on squamous carcinoma cell ORL at IC 50 value of 2. Most of the vitamins have shown controversial results on cancer and further investigation needs to be performed for analyzing their exact roles.
Carotenoids are a macroalgal pigment that includes fucoxanthin, β-carotene, astaxanthin, violaxanthin, capsanthin, siphonaxanthin, lutein, neoxanthin, and others [ ]. Among them, the major carotenoids are the fucoxanthin widely distributed in brown algae Undaria pinnatifida , Laminaria japonica , etc.
The structure of fucoxanthin possesses an allenic bond, a 5,6-monoepoxide, and an acetylated group [ ]. With regard to anticancer activity, fucoxanthin, and fucoxanthinol metabolite induce apoptotic cell death, cell cycle arrest, antiproliferation, and anti-angiogenic effect [ ].
Fucoxanthin exhibits its effect by downregulating MAPK, Bcl-2, MMP-9, and mRNA expression levels of CD44, CXCR4 and stimulation of poly-ADP-ribose polymerase PARP , and caspase-3,-8,-9 [ 1 ].
An analysis by Wang et al. Fucoxanthin was also responsible for the downregulation of the mortalin-p53 complex. On treating with Undaria pinnatifida -derived fucoxanthin, the growth of MDA-MB human breast cancer and tumor-induced lymphangiogenesis were suppressed by reducing the concentrations of VEGF-C, phospho-AKT, VEGF receptor-3, phospho-P13K, NF-κB in human lymphatic endothelial cells.
However, in in vivo MDA-MB nude mouse model micro-lymphatic vascular density micro-LVD was reduced [ ]. Polyphenols are produced by seaweeds to boost their antioxidant properties and act as radical scavengers. They produce polyphenolic compounds including phlorotannins, flavonoids, bromophenols, mycosporin-like amino acids, and phenolic terpenoids [ 1 ].
Phlorotannins are the major polyphenols unique to brown algae [ 20 ] such as kelps, rockweeds, Ecklonia cava , Laminaria japonica , and Sargassacean sp. and comprise a monomeric unit phloroglucinol 1,3,5-trihydroxybenzene [ 1 ].
On the basis of the links between the monomeric units, phlorotannins are divided into four classes: phlorethols and fuhalols ether links , fucols phenyl links , fucophlorethols ether and phenyl links , and eckols and carmalols dibenzodioxin links [ ]. Zenthoefer et al.
The EC 50 value for Panc89 was Also, the inhibitory rate of Panc89 and PancTu1 was Similar to microalgae, many macroalgae-derived components have also been investigated using in silico methods, albeit with very scanty data.
Although caulerpin from Caulerpa racemosa was molecularly docked, it showed that it was an efficient ligand but had a reduced total binding energy when considering whether it could be used as a therapeutic molecule [ ].
Simultaneously, another study of the anticancer activity of metabolites from Caulerpa sp. has been identified as an effective ligand against glucose 6-phosphate dehydrogenase G6PDH and 6-phosphogluconate dehydrogenase 6PGD for targeting the pentose phosphate pathway in colorectal cancer treatment [ ] Fig.
Different algal growth and extraction methodologies for bioactive components, as well as their potential applicability to various cancers and cell lines.
Antimicrobial resistance has rendered many conventional antibiotics ineffective in a number of people with H.
pylori infection [ ]. Antimicrobial resistance to metronidazole, tetracycline, quinolones, clarithromycin, and rifabutin has emerged as a result of gene modulations or mutations, according to molecular investigations [ , ].
As a result, a method to lower cancer's morbidity and mortality has been found in algae with special metabolites that can stop the progression of an H. pylori infection into gastric cancer in the era of multi-drug resistance [ ]. However, there is a scarcity of data on the antibacterial activity of microalgal bioactive components mostly carotenoids against H.
In macroalgae, fucoidan is widely used for its anti- H. pylori activity. Infection with H. pylori raises the risk of gastric and colon cancer. Gastric cancer GC arises from a complicated, multi-step process that starts with normal mucosa and progresses to non-atrophic gastritis.
In a cascade, the progression of superficial gastritis to atrophic gastritis leads to the production of metaplasia, dysplasia, and intestinal-type cancer [ ]. Alongside adhesins, numerous virulence factors vacuolating cytotoxin A VacA , cytotoxin-associated gene A CagA , and urease produced by H.
pylori are integrated into host cells via the type 4 secretory system T4SS within cag pathogenicity island cag PAI for initiating pathogenesis [ , ]. Instead of using bactericidal drugs, antiadhesives can prevent the pathogenesis that results from H. pylori adhering to stomach mucus via lectin-like molecules.
In microalgae, Chlorella sp. and Spirulina sp. These algal polysaccharides have not been shown to impede in vitro bacterial growth, but they can prevent H. In silico analysis of algal peptide interaction with H. pylori suggested peptides from green microalgae Tetradesmus sp.
have been found active inhibitors against three virulent factors Cag A, VacA, and Htr A of H. pylori [ ]. Additional probiotic therapy utilizing the carrageenan-encapsulated Lactobacillus fermentum UCOC strain has demonstrated anti- H. pylori efficacy under fasting conditions pH 3.
Biofilm development, in addition to mutation, enhances bacterial antibiotic resistance. Considering algae's powerful predator defense mechanisms, bioactive substances identified in them are among the most promising sources. Algal extracts have also been shown to degrade the biofilm polymer matrix, resulting in an anti-film effect that, when coupled with antibiotics, prevents bacterial colonization from progressing and developing into gastric cancer [ ].
In addition to genetic and environmental factors, modifications to the stomach adaptive system result in endoplasmic reticulum ER stress, which activates the unfolded protein response and causes precancerous lesions to form at the precancerous stage [ ].
Because pro-apoptotic proteins Bim and Bax are present while VacA interference is present, ER stress causes CHOP transcription, which speeds up apoptosis. Activation of NF-κB, on the other hand, inhibits apoptosis via A20 deubiquitinylase activity, resulting in infection-mediated GC that persists [ , ].
Inflammation has long been a key factor in the development of cancer. Moreover, the ability of human carcinoma MKN45 gastric cells to invade was shown to be inhibited by a new polysaccharide derived from brown algae Sargassum sp. Moreover, porphyran from Porphyra sp. has anticancer characteristics that inhibit in vitro adenocarcinoma cell lines AGS by triggering apoptosis via the mitochondrial pathway [ ].
Apart from dislodging H. pylori from human AGS cells, fucoidan fraction Fucus B has been shown to cause dose-dependent cytotoxicity in AGS cancer cells, which was verified using a lactate dehydrogenase assay.
Additionally, 6 gms of fucoidan taken regularly seems to be non-toxic and has the potential for use in treating H. pylori infection and GC formation [ ]. Furthermore, brown algae sulfated polysaccharides fucoidan have been shown to decrease the expression of IL-1β, IL-6, iNOS, PGE2, NO, and TNF-α.
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pylori in the gastric cells contributes to GC. In addition to CagA's fatal impact, pro-oxidant activities like host spermine oxidase, NADPH oxidase, or mitochondria-mediated ROS production reduce antioxidant or glutathione activity in H.
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Download references. We thank C. Yu, W. Hahn, B. Wolpin, A. Bass, N. Gray, K. Stegmaier, E. Stover, T. Lewis, M. Mesleh, A. Burgin, S. Alper, G. Botta, M. Macaluso, P. Tsvetkov, X. Jin, K. Blakeslee, G.
Ciolek and E. Lander for helpful scientific discussions. Passino, C. Zhu, K. Gore, M. Laird, C. Trapechio and E. Parikh generated the barcoded PRISM cell lines and performed the assays.
Stumbraite assisted with STR fingerprinting. Johnson and J. Davis performed lysate processing and detection. Johnston and R. Singh provided analytical chemistry support. Vrcic, C. Sandland and S.
Figueroa-Lazu assisted with compound management. Kugener and A. Gonzalez provided technical assistance. This study was supported in part by the Carlos Slim Foundation Slim Initiative in Genomic Medicine for the Americas , the Next Generation Fund at the Broad Institute of MIT and Harvard S.
and National Institutes of Health grants nos. U01 HG T. G and A. and K08 CA S. Present address: Department of Human Molecular Genetics and Biochemistry, Tel Aviv University, Tel Aviv, Israel.
Broad Institute of MIT and Harvard, Cambridge, MA, USA. Steven M. Corsello, Rohith T. Nagari, Ryan D. Spangler, Jordan Rossen, Mustafa Kocak, Jordan G.
Bryan, Ranad Humeidi, David Peck, Xiaoyun Wu, Andrew A. Tang, Vickie M. Wang, Samantha A. Bender, Evan Lemire, Rajiv Narayan, Philip Montgomery, Uri Ben-David, Colin W.
Garvie, Yejia Chen, Matthew G. Rees, Nicholas J. Lyons, James M. McFarland, Bang T. Wong, Li Wang, Nancy Dumont, Patrick J. Doench, Caitlin N. Harrington, Heidi Greulich, Matthew Meyerson, Francisca Vazquez, Aravind Subramanian, Jennifer A.
Roth, Joshua A. Bittker, Jesse S. Boehm, Christopher C. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Howard Hughes Medical Institute, Chevy Chase, MD, USA. You can also search for this author in PubMed Google Scholar. and T. conceptualized the study. devised the study methodology. and L. operated the software. and J. validated the data. carried out the formal analysis.
and C. carried out the investigation. managed the resources. and S. curated the data. wrote the original draft. and N. reviewed and edited the draft. and B. oversaw data visualization. supervised the study.
oversaw the project administration. acquired the funding. Correspondence to Todd R. receive research funding unrelated to this project from Bayer HealthCare.
receives research funding from Ono and serves as a scientific advisory board and consultant for OrigiMed. has patents licensed to LabCorp and Bayer. were formerly consultants and equity holders in Foundation Medicine, which was acquired by Roche. is an employee and shareholder of Vertex Pharmaceuticals.
and A. consult for Tango Therapeutics. is a consultant to GlaxoSmithKline and is a founder of Sherlock Biosciences.
Patent applications for the drug uses detailed in this manuscript have been filed. The other authors declare no competing interests. a , Lineage diversity of PRISM cell lines.
Lineages with fewer than 10 cell lines are listed on the right. b , Experimental protocol. Cell lines are grouped by doubling time into pools of approximately 25 cell lines. One pool is plated onto each assay plate. Compounds are transferred by pin transfer from a source compound plate HTS and HTS screens , or cells are plated directly onto assay-ready plates generated by acoustic dispensing of compounds MTS, MTS, and MTS screens.
In either case, compound plates are shared by all replicates of each treatment condition. After incubation and lysis, all assay plates generated by a given compound plate are grouped and collapsed into 3 HTS, MTS, and MTS screens or 6 HTS, MTS screens detection plates so that each detection plate receives 1 or zero copies of each pool.
Ten control barcodes are then spiked into each detection plate well HTS, MTS, and MTS screens. Detection plates are amplified by PCR and detected using Luminex FLEXMAP 3D instruments. c , Data processing workflow. Median Fluorescence Intensity MFI values are calculated from fluorescence values for each replicate-condition-cell line combination and are log2-transformed.
Assay plates wells are normalized, median-collapsed, and compared to the normalized medians of other assay plate wells in the same well position that have been dosed by the same compound plate.
Strictly standardized mean differences SSMD are calculated between positive and negative control conditions for each cell line on each assay plate. In datasets with control barcodes added, data are normalized with respect to the median of control barcodes to generate the MFI normalized data matrix.
Data are DMSO-normalized and pooling artifacts are corrected using ComBat to generate the log fold change data matrix. Up to 3 independently treated plates range based QC filtering in one screen are median-collapsed to generate the collapsed log fold change data matrix.
a , Primary screen QC pass rate by pool. The fraction of treated assay plate-wells that pass the outlier filter is indicated. Cell line log MFI data are median-centered, and the medians of assay plate-wells are compared within each well-detection plate combination.
b , Primary screen QC pass rate by detection plate. c , Primary screen QC pass rate of assay plates. Overall pass rate was high median d , Secondary screen QC pass rate by pool.
e , Secondary screen QC pass rate by detection plate. f , Secondary screen QC pass rate by plate-pool combinations. Across the screen, 5. aa , Primary screen QC pass rate by cell line.
Muscular endurance benefits of cancer Fitness and Agility increased sharply throughout pootential world. The Anticancwr Anticancer potential finding a targeted Anticqncer drug takes a long time and potentual lot of money. One method that Anticancer potential help overcome this is computational methods, such as virtual screening. It can be an important alternative in early-stage drug discovery. The aim of this study is to explore and analyze the potential protein targets of Bajakah tampala Spatholobulus littoralis as an anticancer chemotherapy. This is a bioinformatics study that uses the in silico method through the pathway analysis method with PubChem software, Swiss Target prediction, String and Cytoscope.
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