Curcumin and Breast Cancer -
Read on to learn more. Curcumin is the active compound found in turmeric , a member of the ginger family. Turmeric is a common spice used in traditional Indian cooking, especially in curry powder, and has long been used in Ayurvedic and Chinese medicine.
Known for its bright yellow color, consuming turmeric as a supplement or in foods has been associated with good health for centuries — and for good reason. As a compound, curcumin has been shown to have positive health effects on many parts of the body.
Some studies have shown curcumin may be used to combat breast cancer in several ways, including:. Estrogen is a reproductive hormone that plays a role in the growth and spread of an estimated 70 percent of breast cancer types.
A report even showed that curcumin may also be useful in keeping breast cancer stem cells from forming. This is an important step in preventing breast cancer from recurring in people who have already managed the disease. Curcumin is a polyphenol compound that is unstable in many other substances.
Clinical studies are being done to investigate curcumin as a stand-alone treatment monotherapy or a combination therapy in treating breast cancer. Some examples include:. Curcumin found in turmeric may enhance the efficiency of chemotherapies in treating cancer while also reducing unwanted or unpleasant side effects of these treatments.
This was suggested in a review in the journal Molecules that looked specifically at curcumin combination chemotherapy. Outside of the benefits specifically related to cancer, curcumin has also been credited with protecting physical health in other ways that could help your body fight cancer.
Curcumin has been credited as an:. In Ayurvedic and Chinese medicine, turmeric is often used to help treat:. Until more research is done, curcumin and turmeric should only be considered as a complementary therapy to proven treatments.
Experts caution that these kinds of integrative therapies should not be used to replace or delay standard, proven therapies used in cancer treatment. Integrative medicine is widely used to treat many conditions, especially cancer. These treatments may provide additional therapeutic benefits alongside standard treatments, like the use of ginger in relieving nausea caused by chemotherapy.
Diet changes and nutritional supplements are popular forms of integrative treatment, and turmeric is usually included. Turmeric can also react with a number of other medications, supplements, or medical conditions. Possible negative side effects or reactions of turmeric can include:.
Turmeric is a flowering plant that grows in tropical climates. To use as a spice or medicinally, the root of the turmeric plant is dried and chopped up or ground into a fine powder.
You can typically buy turmeric in chopped or powdered form at many markets and grocery stores. When used in cooking, this powder can be directly added into foods for flavor or color.
When used medicinally or as a nutritional supplement, the general consensus is that between to 2, milligrams mg per day is enough. But turmeric is sold in a number of ways that can be added into your diet without eating it in your foods. Liquid extracts are the most potent, but you can purchase turmeric supplements in capsules, pills, and gummies.
Breast cancer can be passed down in families through genetic mutations that increase your risk of developing breast cancer, especially in combination with lifestyle or environmental factors.
Talk with a doctor if you know that a form of inherited breast cancer runs in your family. A doctor can help you take steps to prevent breast cancer by recommending:. Research suggests that curcumin found in turmeric can have a lot of healthy benefits, including the potential to fight or even prevent breast cancer and other cancers.
Speak with a doctor before you take turmeric or any other supplements. While these supplements may help, there are many aspects involved in a successful cancer treatment plan. Our experts continually monitor the health and wellness space, and we update our articles when new information becomes available.
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Knowing your breast cancer risk can be an important first step in taking care of your health. Curcumin administered at different concentrations and via different routes of administration inhibited proliferation, decreased viability, and induced apoptosis in human and animal breast cancer cells.
Nanoparticle formulations of curcumin administered orally, via implant, and intraperitoneally reduced the tumor volume of human and murine mammary cells in vivo.
Moreover, curcumin nanoformulations exert positive effects on tumor growth inhibition in animal models of breast cancer. Further randomized clinical trials are warranted to assess the efficacy and safety of curcumin formulations for clinical use.
Keywords: anticancer; breast tumor; in vitro; in vivo; nanoparticles; turmeric. Abstract Breast cancer is one of the most common neoplasms among women.
Curcumin and Breast Cancer cancer is the Low-calorie beverages leading Bresat of cancer-associated mortality Optimal nutrition choices for pre-event hydration women in Curcumin and Breast Cancer world 12. Current therapeutic strategies Cahcer breast Beast, which include surgery, chemotherapy and radiotherapy, may Curcumni efficacy due to a high risk of Curcumin and Breast Cancer, Weight management plans patient response and the emergence of Curcunin Curcumin and Breast Cancer 3. This supports the requirement to understand Cancef genetic and biochemical Cancre underlying the uncontrolled cell proliferation in breast cancer, in order to develop novel therapies. In breast cancer tissues, the overexpression of cyclin-dependent kinases CDKs and underexpression of tumor suppressor protein p53 is frequently observed 4. Simultaneously, a number of cell cycle regulatory proteins are downregulated, including the CDK inhibitors, p21, p27 and p57 5 — 8. Targeting these molecules may be effective in breast cancer therapy 5and natural products that target these molecules are particularly attractive as they are likely to have high therapeutic potential and less likely to induce adverse effects 9 Plants are an excellent source of bioactive natural compounds 711 — 13and polyphenolic compounds from plants frequently exert multiple therapeutic effects 14 —Curcumin and Breast Cancer -
In total, 60 articles met the inclusion criteria. Curcumin administered at different concentrations and via different routes of administration inhibited proliferation, decreased viability, and induced apoptosis in human and animal breast cancer cells.
Nanoparticle formulations of curcumin administered orally, via implant, and intraperitoneally reduced the tumor volume of human and murine mammary cells in vivo. Moreover, curcumin nanoformulations exert positive effects on tumor growth inhibition in animal models of breast cancer.
Further randomized clinical trials are warranted to assess the efficacy and safety of curcumin formulations for clinical use. Keywords: anticancer; breast tumor; in vitro; in vivo; nanoparticles; turmeric. By itself, curcumin had a minimal impact on ROS in vehicle-treated MCF-7 cells, but treatment with camptothecin induced a 2.
When curcumin was present in conjunction with either of these two chemotherapeutic agents, it inhibited ROS generation in a dose-dependent fashion.
In the case of mechlorethamine, for example, 1, 5, and 10 μ m curcumin inhibited induction of ROS by A similar trend was noted in BT cells in which curcumin inhibited ROS by ROS have been reported to stimulate SAPK pathways such as JNK 47, 48 , and because curcumin inhibits JNK and AP-1 signaling 16, 17 , we sought to determine its impact on chemotherapy-induced JNK activation.
Using an in vitro immunocomplex assay, curcumin appeared to have the ability to inhibit JNK activation in a dose-dependent fashion in MCF-7 cells treated with camptothecin data not shown. To characterize this further, AP-1 activity was probed using an ELISA that detects phospho-c-Jun levels.
By itself, curcumin had a mild impact on AP-1 in vehicle-treated MCF-7 cells, but treatment with mechlorethamine induced a 1.
When curcumin was present with either of these two agents, it inhibited AP-1 activation, and in most cases did so in a dose-dependent fashion. In the case of camptothecin, for example, 1, 5, and 10 μ m curcumin inhibited AP-1 activation by A similar trend was noted in camptothecin-treated BT cells in which curcumin inhibited AP-1 activation by Because ROS reviewed in Ref.
Thus, the cytosolic fractions from cells were isolated, and the presence of cytochrome c was determined by Western blotting. Both camptothecin and mechlorethamine induced large amounts of cytochrome c release into the cytosol of MCF-7 cells, compared with vehicle-treated controls Fig.
However, curcumin was able, in a dose-dependent fashion, to decrease the levels of cytosolic cytochrome c. These studies support the hypothesis that curcumin inhibits topoisomerase 1 inhibitor- and alkylating agent-mediated apoptosis by inhibiting ROS generation, JNK activation, and mitochondrial cytochrome c release.
The ability of curcumin to inhibit chemotherapy-mediated apoptosis in culture suggested that it might have the same activity in vivo. This represents 8. Twenty-four h later, these mice were treated with a single injection of cyclophosphamide, an alkylating agent that is a component of several regimens used to treat patients with breast cancer, and the impact on their tumors was followed daily for 2 days.
In pilot experiments with both MCFbased and BTbased xenografts, the animals receiving a regular diet treated with cyclophosphamide had a significant decrease in tumor size from the day of treatment, or day 1, to day 2.
The animals receiving a curcumin-supplemented diet treated with cyclophosphamide, however, did not have a significant decrease in tumor size over this time period. Power calculations were then performed to determine the sample size needed to obtain statistically significant results, and a second study was performed using the BT model system.
Animals treated with cyclophosphamide feeding on a standard diet had a significant decrease in their tumor size from day 1 to day 2, after which the tumors began growing once again Fig. When animals feeding on a curcumin-supplemented diet were treated with cyclophosphamide, however, their tumors did not decrease in size and continued to grow from day 1 to day 2 and then to day 3 Fig.
Indeed, whereas tumors in the standard diet group had increased by only 1. In contrast, control experiments showed no such differences in vehicle-treated animals data not shown , with tumors in the standard diet group increasing by 2. To determine whether the decreased effectiveness of cyclophosphamide was attributable to inhibition of programmed cell death, tumor sections were prepared 24 h after cyclophosphamide.
Apoptosis was then evaluated by probing for single-stranded sequences after formamide-induced DNA denaturation 35 , and densitometry was performed to obtain quantitative results.
Comparing the two cyclophosphamide-treated groups, there was 1. Also, whereas cyclophosphamide increased apoptosis in the standard diet group compared with treatment with vehicle alone, in the curcumin diet group it did not increase the abundance of ssDNA data not shown. Treatment of the standard diet group with cyclophosphamide resulted in a significant increase in phospho-JNK reactivity Fig.
Indeed, this latter group showed no increased fluorescence density compared with that of the vehicle-treated curcumin diet group or the vehicle-treated standard diet group.
These studies support the hypothesis that in vivo , as it does in tissue culture, curcumin can inhibit alkylating agent-induced apoptosis and JNK activation. The chemopreventive activity of curcumin in several animal tumor model systems has led investigators to examine its potential impact on apoptosis with varying results.
Some reports suggest that curcumin inhibits apoptosis such as in human and rat T lymphocytes 30 , whereas others have documented an induction of apoptosis in lines such as HL60 cells 29 and in vivo in azoxymethane-induced colon tumors In some cell lines, there have even been conflicting results such as in HT human colon cancer cells that have been noted to be induced into apoptosis by some 53 , whereas others have noted no effect of curcumin With respect to cytotoxic chemotherapy, curcumin has been reported to protect rat lungs and myocardium from injury by bleomycin 31 and Adriamycin 32 , respectively, and inhibit apoptosis in UV-irradiated Jurkat cells and dexamethasone-treated thymocytes 54 , but it could not inhibit etoposide-induced apoptosis in U human monoblastic leukemia cells Many of these investigations have used extended incubation periods with very high curcumin concentrations, however, that would be unlikely to be achieved as a result of dietary curcumin intake by cancer patients.
Therefore, we sought to study the effects of curcumin using conditions that more closely reproduced those that could be found in vivo.
Because of its ability to act as a free radical scavenger 6, 7, 8 and to inhibit AP-1 16 and JNK activation 17 , we hypothesized that because these are important steps in the ability of some cytotoxic DNA-damaging drugs to induce apoptosis, dietary curcumin might inhibit the effectiveness of such cancer chemotherapy.
In this study, we demonstrate that curcumin was able, in a dose- and time-dependent fashion, to inhibit camptothecin-mediated apoptosis in MCF-7 breast cancer cells Fig. This occurred at concentrations that have been documented in a Phase I chemoprevention trial in humans, where serum curcumin levels ranging from 0.
Serum levels in humans after an oral dose of curcumin peak rapidly in as little as 1—2 h, but they decline much more slowly over the next 12 h 25 , and in our studies, even a brief 3-h exposure to curcumin was sufficient to significantly inhibit apoptosis.
Moreover, this inhibition was demonstrable in a concentration-dependent manner using the topoisomerase 1 inhibitor camptothecin, the alkylating agent mechlorethamine, and the anthracycline Adriamycin, not only in MCF-7 cells but also in MDA-MB and BT human breast cancer cells.
Such findings suggest that this activity is independent of p53 status because MCF-7 cells are p53 wild type, whereas MDA-MB and BT cells have mutant p Hormone receptor status would also appear to not be a significant influence because MCF-7 cells are estrogen receptor positive, whereas MDA-MB cells are receptor negative However, additional experiments, e.
To evaluate possible mechanisms responsible for this inhibition of apoptosis, we studied ROS generation and found that curcumin could, in a dose-dependent fashion, inhibit the camptothecin- and mechlorethamine-induced production of ROS Fig.
JNK activation with AP-1 activity Fig. These findings support the hypothesis that curcumin inhibits apoptosis by blocking ROS formation and JNK activation, both of which are important signals for cytochrome c release from mitochondria into the cytoplasm, which triggers caspase-mediated programmed cell death.
If confirmed, such a mechanism would allow the prediction that drugs that do not activate JNK should not be influenced by curcumin. Consistent with this assumption, methotrexate and 5-fluorouracil, two drugs used in the care of breast cancer patients, which function as antimetabolites and are not known to activate JNK, were able to induce apoptosis without any impact by curcumin data not shown.
It should be noted, however, that Bhaumik et al. This difference may be attributable to the experimental conditions because Bhaumik et al. used a concentration of 50 μ m curcumin and did not study its impact in the presence of a chemotherapeutic agent.
Alternatively, this may indicate that there is some cell type specificity to the impact of curcumin. The current studies also do not rule out a possible involvement of other pathways that are impacted upon by curcumin in blocking apoptosis.
For example, activation of the transcription factor NF-κB is important in paclitaxel-induced apoptosis 58 , and because curcumin inhibits NF-κB 14, 15 , this may be another pathway involved in its antiapoptotic activity.
Additional ongoing studies using dominant negative mutant constructs that will selectively inactivate only one pathway at a time will hopefully prove instructive in elucidating the molecular basis for this function of curcumin. Given the ability of curcumin to inhibit apoptosis in tissue culture, we sought to determine whether it could also do so in vivo , and we found that dietary supplementation significantly decreased cyclophosphamide-induced tumor growth delay Fig.
Immunofluorescence studies indicated that this occurred in conjunction with decreased apoptosis and also with decreased JNK activation Fig.
This result was somewhat surprising in that, whereas serum curcumin concentrations in chemoprevention trials have been comparable with those used in our in vitro studies, these occurred at a daily curcumin dose of mg Even in populations where dietary curcumin intake is high, daily exposure is only on the order of mg 1, 2, 3, 4.
Therefore, it might seem unlikely that such diets would result in systemic curcumin levels approaching the conditions we used in vitro , especially since the oral bioavailability of curcumin is low because it is extensively metabolized by the liver.
Studies of tumor sections, however, revealed that those from the two curcumin-supplemented diet groups showed an immunofluorescence characteristic of curcumin, whereas the standard diet groups did not data not shown; Refs.
This supports the possibility that, even after only short-term feeding, curcumin, or one of its metabolites, can be present in tumor tissue. One possible explanation for the ability of dietary curcumin to inhibit apoptosis at low levels of exposure in vivo is that this may represent a difference in the absorption and metabolism of curcumin between humans and animals.
A recent study comparing human and rat hepatocytes, however, found that the major metabolites in both were hexahydrocurcumin and hexahydrocurcuminol Alternatively, although curcumin metabolites have been shown to be less able to inhibit phorbol ester-induced prostaglandin E 2 production in human colonic epithelial cells than the parental compound 59 , they may be more active than curcumin in their ability to inhibit ROS formation, JNK activity, and cytochrome c release.
Finally, it is possible that some of the antiapoptotic effect of curcumin in vivo does not require it to be present at the site of the tumor. Cyclophosphamide is a prodrug activated by cytochrome Ps in the liver 45 , and curcumin inhibits several P isoenzymes The higher concentrations of curcumin one would expect to find in the liver after a meal containing this agent may be sufficient to inhibit conversion of cyclophosphamide to its active metabolites, thereby limiting its antitumor efficacy.
Because curcumin has antiangiogenic properties and may have therapeutic potential in human prostate cancer 24 , our findings also suggest care in its application to patients with other malignancies receiving concurrent chemotherapy until this activity of curcumin can be further investigated.
It is possible, therefore, that the effects of curcumin might be amplified in patients with colon cancer receiving chemotherapy unless, as noted above, it has some cell type specificity, or its antiapoptotic effects are mediated through hepatic cytochrome P Finally, these findings strongly support additional research to determine whether breast cancer, and possibly other cancer patients undergoing chemotherapy, should limit dietary supplementation of curcumin, which is widely available over the counter as turmeric extracts, and possibly even avoid curcumin-containing foods altogether.
Curcumin inhibits camptothecin-induced apoptosis in MCF-7 cells. A , MCF-7 breast carcinoma cells were exposed for 12 h to either vehicle Lane 3 , 10 μ m curcumin Lane 4 , 10 μ m camptothecin Lane 5 , or both camptothecin and curcumin Lane 6 , and compared with mock-treated cells Lane 2.
Apoptosis-associated DNA fragmentation was evaluated by agarose gel electrophoresis with λ digested with Hin dIII Lane 1 and a bp ladder Lane 7 as standards. B , after MCF-7 cells were treated with vehicle, curcumin, camptothecin, or curcumin and camptothecin, apoptosis was evaluated using the Cell Death Detection ELISA PLUS kit.
Results are the mean and SE from four experiments expressed as the fold increase in apoptosis compared with the vehicle control, arbitrarily set at 1. C , caspase 3 activity assays were performed on MCF-7 cells using the substrate acetyl-aspartyl-glutamyl-valyl-aspartate.
Results are the mean ± SE from three experiments, expressed as the ratio of absorbance of each sample to that of the vehicle control, arbitrarily set at 1. D , time dependence was studied by treating MCF-7 cells with Curcumin was either preincubated for 3 h and then present throughout camptothecin treatment for a total of 15 h, added at the same time as camptothecin, or at 3-h intervals thereafter.
The mean percentage inhibition ± SE is shown from four experiments. Curcumin inhibits generation of ROS. MCF-7 A and BT B cells were either mock treated, vehicle treated, or exposed to curcumin at 1, 5, and 10 μ m. In parallel, they were exposed to either 10 μ m camptothecin or μ m mechlorethamine, with or without curcumin, for 12 h.
The mean ± SE is shown from three experiments, each performed in duplicate. Curcumin inhibits JNK activation. MCF-7 A and BT B cells were treated as described in the legend to Fig. The mean ± SE is shown from two experiments, each performed in duplicate, with results expressed in relation to vehicle-only controls, which were arbitrarily set at 1.
Curcumin inhibits release of cytochrome c into the cytosol. MCF-7 cells were treated with vehicle and camptothecin A or mechlorethamine B either alone or in the presence of curcumin. The content of cytochrome c in the cytosol was evaluated by Western blotting, and equal loading was confirmed by reprobing each blot for heat shock cognate protein Densitometry of the autoradiographs was performed for cytochrome c levels, corrected for loading, and the data are shown below each panel in relation to the chemotherapy agent alone, which was arbitrarily set at 1.
BT cells were similarly treated in C and D , respectively, and each panel is a representative result from one of two experiments. V , vehicle; Cam , camptothecin; Mech , mechlorethamine. Dietary curcumin blunts cyclophosphamide-mediated tumor growth inhibition.
Nude mice bearing BTbased xenografts were randomized on day 0 to receive either standard or curcumin-supplemented diets and on day 1 were treated with a single i. Tumor weights were followed for a total of 3 days, calculated using the tumor dimensions, and plotted as the ratio of the tumor weight to that on day 0, which is arbitrarily set at 1.
Sixteen mice were included in each of these treatment groups, whereas two additional groups were treated with either a standard diet and vehicle or the curcumin-supplemented diet and vehicle. These results are described in the text. Dietary curcumin inhibits apoptosis and JNK activation in vivo. One day after treatment with cyclophosphamide, BTbased tumor xenografts were excised, sectioned, and prepared for immunofluorescence.
Apoptosis induced by cyclophosphamide is shown in the standard diet group A and in the curcumin-supplemented diet group B as red areas containing ssDNA. Phospho-JNK staining is shown in C and D for these two groups, respectively, with red areas indicating presence of phosphorylated, activated JNK.
Control slides from vehicle-treated standard diet and curcumin diet groups were prepared as well. The density of immunofluorescence staining discussed in the text is the mean from five separate fields on two duplicate slides. The costs of publication of this article were defrayed in part by the payment of page charges.
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Skip Nav Destination Close navigation menu Article navigation. Volume 62, Issue Previous Article Next Article. MATERIALS AND METHODS. Article Navigation. Tumor Biology July 01 Dietary Curcumin Inhibits Chemotherapy-induced Apoptosis in Models of Human Breast Cancer 1 Sivagurunathan Somasundaram ; Sivagurunathan Somasundaram.
The Lineberger Comprehensive Cancer Center [S. This Site. Google Scholar. Natalie A. Edmund ; Natalie A. Dominic T. Moore ; Dominic T. George W. Small ; George W.
Yue Y. Shi ; Yue Y. Robert Z. Orlowski Robert Z. Received: February 15 Accepted: April 25 Online ISSN: Cancer Res 62 13 : — Article history Received:. Cite Icon Cite.
toolbar search Search Dropdown Menu. toolbar search search input Search input auto suggest. View large Download slide. Curcumin concentration. Breast cancer cell line. Camptothecin 1 μ m 9. a All results are the mean and SE from four experiments.
b ND, not done. View Large. Pharmacology of Curcuma longa. Planta Med. Clinical development plan: curcumin. Recent studies on the biofunctions and biotransformations of curcumin.
Cytotoxicity and cytoprotective activities of natural compounds. The case of curcumin. Estimation of the distribution of the maximum theoretical intake for ten additives in France.
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To Breawt requests for reprints should be addressed, at Energy snack bars University of Curcumin and Breast Cancer Carolina at Chapel Hill, Lineberger Comprehensive Cancer Center, CBMason Farm Road, Chapel Hill, NC Sivagurunathan SomasundaramNatalie A. EdmundDominic T. MooreGeorge W. SmallYue Y. Curccumin Curcumin and Breast Cancer Breash one WHR and psychological well-being Curcumin and Breast Cancer most common neoplasms among women. Caner strategies using natural formulations and phytotherapies are promising Cacer treatment alternatives. This review assesses the antitumor effects of curcumin on breast cancer reported in preclinical in vitro and in vivo animal models. We used five databases to search for preclinical studies published up to May The assessments included the effects of curcumin on the proliferation, viability, and apoptosis of breast cancer cell lineages and on tumor volume. In total, 60 articles met the inclusion criteria.
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