Turmeric is recommended for breast cancer
Turmeric is a bright yellow spice made from the dried rhizome (underground stem) of the plant Curcuma longa that is used extensively in Indian cooking. Biologically active components of turmeric include curcumin and various turmerones. Turmeric and its components have been shown to have antioxidant, anti-inflammatory, antibacterial, antifungal, antiparasitic, anti-thrombotic, anti-proliferative, anti-angiogenic, radioprotective, neuroprotective and cardioprotective effects.Curcumin has been shown to inhibit proliferation and induce apoptosis of chronic and acute myeloid leukemia, Burkitt’s lymphoma, melanoma, osteosarcoma, head and neck squamous cell, esophageal, brain, thyroid, lung, synovial, pancreatic, liver, intestinal, colorectal, endometrial, cervical, bladder, ovarian, and prostate cancer cells. Although turmeric contains up to 5% curcumin, the bioavailability of curcumin in turmeric is limited, apparently because of poor absorption and rapid elimination from the body. Therefore, the levels of curcumin used in laboratory experiments to assess its chemoprotective effects typically are many times higher than that which would be result from consuming turmeric in the diet.
Breast cancer-related effects of consuming turmeric
Curcumin has been shown in the laboratory to have profound and diverse effects on breast cancer carcinogenesis, proliferation and metastasis. Furthermore, these anticancer actions have been observed against several types of breast cancer, including estrogen receptor-positive and progesterone receptor-positive (ER+/PR+), ER-negative and PR-negative (ER-/PR-), and HER-2/neu overexpressing cell lines. Some degree of selectivity for cancer cells also has been observed.
Adding curcumin to chemotherapy regimes that include Taxol (paclitaxel) or Adriamycin (doxorubicin) has been shown to enhance their cytotoxicity. Curcumin also has been shown to be an iron chelator, which may be helpful in reducing iron for some women (since high stores of iron can contribute to breast cancer risk), but could negatively impact women with marginal stores of iron or those undergoing chemotherapy.
Curcumin has been found in mouse models to effectively protect skin from radiation damage, while at the same time sensitizing breast cancer cells to radiation and making them more susceptible to its effects. Therefore, it appears that adding turmeric to the diet during radiation treatment does not lessen the radiation's effectiveness and could be beneficial. Also, there is some evidence that turmeric could help protect normal breast cells from radiation-induced cancer (e.g., when radiation is used to treat other cancers).
Curcumin has been shown to inhibit progestin-accelerated mammary tumors in rats. Combined hormone therapy containing both estrogen and progestin has been found to result in increased risk of breast cancer in postmenopausal women. Treatment with curcumin was found to postpone the first appearance of progestin-accelerated tumors, decrease overall tumor incidence, and reduce proliferation. These results suggest that curcumin might be an effective a dietary chemopreventive agent in women already exposed to combined hormone therapy.
While the in vitro and in vivo evidence of curcumin's anti-cancer activities is remarkable, there have been no population studies that specifically address the association between turmeric consumption and the risk of breast cancer (or other cancers). India, where turmeric is a dietary staple, has lower overall cancer rates and breast cancer rates than countries in the west (although the rates are rising, particularly in urban areas). One 2005 study found that south Asian women (having origins mainly in India, Pakistan, Bangladesh and Sri Lanka) living in California were 3.5 times more likely to develop breast cancer than native Asian Indian females. However, these results likely are the result of a variety of non-dietary as well as various dietary factors. The lack of population studies with respect to turmeric intake lead us to rate this spice as "recommended" for breast cancer rather than "highly recommended."
Additional comments
While curcumin has been shown to have a cytotoxic impact on microbes such as the malaria parasite Plasmodium falciparum, one study also showed that long-term use of low-dose curcumin supplementation suppressed immunity against some other microbes (i.e., pathogens whose elimination primarily involves reactive radicals generated from inflammation).
Consuming black pepper along with turmeric may enhance the spice's anti-breast cancer action by enhancing breast stem cell sensitivity to curcumin.
Consumption of supplemental turmeric has been shown to increase urinary oxalate excretion, leading to a greater risk of kidney stones in susceptible individuals. Turmeric might interfere with Warfarin (coumadin) and other blood-thinning therapy since it has been shown to reduce thrombosis formation.
Selected studies
Targeting breast stem cells with the cancer preventive compounds curcumin and piperine Breast Cancer Research and Treatment, November 2009The present study was designed to investigate whether the dietary polyphenols curcumin and piperine influence the self-renewal of normal and malignant breast stem cells. Currently available breast cancer preventives typically only reduce the incidence of hormonally driven cancer. According to the cancer stem cell hypothesis, malignancies arise in stem and/or progenitor cells through the dysregulation or acquisition of self-renewal, offering another potential pathway to reduce malignancy. The study examined the effects of curcumin (found in turmeric) and piperine (found in black pepper) on mammosphere formation, expression of the breast stem cell marker aldehyde dehydrogenase, and Wnt signaling. Wnt proteins are signaling molecules that regulate certain cell-to-cell interactions such as embryogenesis. Both curcumin and piperine were found to inhibit mammosphere formation, serial passaging, and percent of aldehyde dehydrogenase+ cells by approximately 50% at 5 μM and entirely at 10 μM concentration in both normal and malignant breast cells. No effect on cellular differentiation was observed. Curcumin and piperine both inhibited Wnt signaling by 50% at 5 μM and entirely at 10 μM. Curcumin and piperine both separately and in combination were found to reduce breast stem cell self-renewal but not to cause toxicity to differentiated cells. In fact, piperine enhanced the effects of curcumin. In other words, they decreased the number of stem cells while having no effect on normal differentiated breast cells. The authors conclude that these compounds could be potential cancer preventive agents.
Curcumin inhibits cell proliferation of MDA-MB-231 and BT-483 breast cancer cells mediated by down-regulation of NFκB, cyclinD and MMP-1 transcription Phytomedicine, October 2009
The present study was designed to investigate the mechanisms by which curcumin, an active constituent of turmeric, inhibits breast cancer cell growth. Curcumin has been reported to inhibit cell proliferation and induce apoptosis of a board range of cancer cells. In the study, the authors examined the effect of curcumin on NFκB, cell cycle regulatory proteins, and matrix metalloproteinases in MDA-MB-231 and BT-483 breast cancer cells. Cell proliferation, the activity of matrix metalloproteinase-1, 3, 9, cell cycle regulatory proteins, and the expression of NFκB in breast cancer cells all were assessed. Curcumin was found to inhibit proliferation of MDA-MB-231 and BT-483 cells in a time- and dose-dependent manner. Treatment with curcumin resulted in reductions in the expression of cyclin D1 in MDA-MB-231 cells and the expression of CDK4 in BT-483 cells. Compared with untreated cells, matrix metalloproteinase1 mRNA expression declined significantly in curcumin treated BT-483 and MDA-MB-231 cells. The authors conclude that curcumin reduces proliferation and invasion by down-regulating NFκB inducing genes.
Curcumin delays development of medroxyprogesterone acetate-accelerated 7,12-dimethylbenz[a]anthracene-induced mammary tumors Menopause, July 2009
The current study was designed to examine whether curcumin, an Indian spice derived from the turmeric root, inhibits carcinogen-induced, progestin-accelerated mammary tumors in Sprague-Dawley rats. Combined hormone therapy containing both estrogen and progestin (medroxyprogesterone acetate) has been found to result in increased risk of breast cancer in postmenopausal women, compared with hormone therapy regimens containing estrogen alone or placebo. The authors previously had reported that progestin can accelerate the development of mammary tumors in animals by increasing vascular endothelial growth factor (VEGF) levels and that curcumin specifically inhibits progestin-induced VEGF secretion from breast cancer cells in vitro. In the study, 55-day old virgin female Sprague-Dawley rats were given the carcinogen 7,12-dimethylbenz[a]anthracene (DMBA) (20 mg/rat) on day zero. On day 30, 60-day timed-release pellets containing 25 mg progestin were implanted into the rats. Curcumin was administered at a rate of 200 mg per kg daily from days 26 to 50, and the animals were sacrificed on day 52. There were 15 to 19 animals per group (i.e., treatment and control groups). Treatment with curcumin was found to postpone the first appearance of progestin-accelerated tumors by seven days. In addition, in the curcumin-treated group, there was a lower overall tumor incidence by the end of the experiment and reduced tumor multiplicity. Curcumin also was found to prevent many of the histological changes observed in the progestin-treated mammary glands. Immunohistochemical analyses of the mammary tumors showed that curcumin inhibited progestin-induced VEGF induction in hyperplastic lesions, although it did not alter the levels of estrogen and progesterone receptors. The authors suggest that curcumin be tested as a dietary chemopreventive agent in women already exposed to progestin to decrease or delay the risk of breast cancer associated with combined hormone therapy.
Curcumin inhibits proliferation, invasion, angiogenesis and metastasis of different cancers through interaction with multiple cell signaling proteins Cancer Letters, October 2008
Since most cancers are the result of dysregulation of up to 500 different genes, treatments that target multiple gene products are needed for cancer prevention and treatment. Curcumin, the compound in turmeric responsible for its yellow color, has been shown to interact with, and modify the expression and activities of, a wide variety of proteins. These include inflammatory compounds, transcription factors, and gene products linked to cell death and survival, proliferation, invasion, and angiogenesis. Curcumin has been found to inhibit the proliferation of various cancer cells in vitro, prevent carcinogen-induced cancers in laboratory animals, and inhibit the growth of human tumor transplants in animal models alone and in combination with several chemotherapy drugs and radiation treatment. The authors note that several phase I and phase II clinical trials indicate that curcumin is quite safe and may exhibit therapeutic efficacy.
The anti-metastatic effect of the chemopreventive polyphenol Curcumin - in vitro and in vivo studies on the molecular mechanisms American Association for Cancer Research (AACR) Meeting, April 2008
The current study was designed to test the hypothesis that curcumin is useful for breast cancer chemoprevention by inhibiting the formation of breast cancer metastases. Metastatic cells probably are disseminated in the body long before detection of the primary tumor leads to cancer diagnosis. Therefore, metastasis during early phases of carcinogenesis in high risk women is a potential prevention target. Curcumin has been found to reduce the activity of Nuclear Factor kappa B (NFB), an inflammation- and cell survival-related transcription factor, although the suppression of NFB cannot be the only reason for curcumin's anti-metastatic effect. The authors examined both the in vitro effects of curcumin on MDA-MB-231 human breast cancer cells and the in vivo activities of curcumin in a mouse metastasis model. Curcumin was found to strongly induce apoptosis in the estrogen receptor-negative and progesterone receptor-negative (ER-,PR-) MDA-MB-231 breast cancer cells, in concert with diminished activation of NFB. In addition, the breast cancer cells were found to have less invasive capacity. Application of curcumin in immunodeficient mice was found to result in significantly fewer lung metastases after intracardiac injection of MDA-MB-231 cells (p=0.0035); 68% of the curcumin treated mice but only 17% of the control untreated mice developed no or very few lung metastases. The authors also used microarray gene expression analyses to develop a more complete understanding of the effects of curcumin on breast cancer cells. Among the 62 genes whose expression was found to be significantly altered by curcumin, two inflammatory cytokines, CXCL1 and CXCL2, were found to be down-regulated. Further analysis showed that curcumin impaired the expression of CXCL1 and 2 and reduced their mRNA levels in a way that was NFB dependent and required intact IB expression. Moreover, CXCL1 and CXCL2 silencing lead to down-regulation of several metastasis-promoting genes, among which was the cytokine receptor CXCR4. The authors therefore suggest that the decrease of CXCL1 and CXCL2 mediated by curcumin is involved in the inhibition of metastasis. The data also demonstrated that curcumin had anti-proliferative and pro-apoptotic effects and thereby reduced the metastatic dissemination of tumor cells, most likely by means of down-regulation of NFB dependent transcription. The authors conclude that dietary chemoprevention of metastases appears feasible.
Curcumin: A treatment for breast cancer and radiation-induced dermatitis American Association for Cancer Research (AACR) Meeting, April 2008
The present study was designed to evaluate the ability of curcumin to act as a radioprotector of skin and as radiosensitizer in human breast cancer cells. Radiation treatment for breast cancer typically damages surrounding normal cells and tissues and skin reactions occur in the majority of patients. Curcumin, a major component of turmeric and curry powders, is known to have potent anti-inflammatory and antioxidant, as well as radioprotective and radiosensitizing properties. Since tumors, unlike non-cancerous tissues, thrive in an environment with high inflammation and high levels of growth and angiogenic factors, curcumin is thought to successfully reduce inflammation and breast cancer growth without adversely affecting normal tissues. To test the effect of curcumin on radiation treatment, SKH-1 hairless mice were administered curcumin (200mg/kg) or placebo (corn oil) intragastrically before or after irradiation with 30 Gy to the left hind leg. After 14 days, radiation-induced dermatitis was observed in all the mice, except for those that had received curcumin after radiation. In a second group of studies, C3H mice were used to determine whether curcumin affected the growth of mouse mammary tumors. Intragastric and intraperitonal administration of curcumin was found to reduce Mca4 and Mca35 mammary tumor growth by 50% in C3H mice. Finally, 5 human breast cancer cells lines (MDA-MB-231, MCF-7, MDA-MB-453, BT-20, SK-BR-3) and immortalized human mammary cell line MCF-12A were treated with 2µM or 5µM curcumin both in the presence and in the absence of radiation (2 Gy or 4 Gy). Curcumin combined with radiation was found to inhibit survival of all 5 breast cancer cell lines. In addition, curcumin combined with radiation reduced the invasiveness of MDA-MB-231 and BT-20 cells. The authors concluded that curcumin effectively protected skin from radiation damage, while sensitizing breast cancer cells to radiation.
The potentiation of curcumin on insulin-like growth factor-1 action in MCF-7 human breast carcinoma cells Life Sciences, May 2007
The present study was designed to investigate whether the growth inhibitory effects of curcumin are related to changes of the insulin-like growth factor-1 (IGF-1) system in MCF-7 human breast cancer cells. In vitro studies have shown that curcumin inhibits cell growth and induces apoptosis in MCF-7 cells. The IGF-1 system, including IGF-1 and IGF-2, IGF-1 receptor (IGF-1R) and IGF binding proteins (IGFBPs), appear to play a critical role in the development of breast cancer. IGF-1 at 50 μg/l in serum-free medium was found to produce maximum proliferation while minimizing apoptosis. However, curcumin was shown to have a potent ability to reduce IGF-1-stimulated MCF-7 cell growth and to reverse IGF-1-induced resistance to apoptosis. To determine whether curcumin intervenes with IGF-1 or IGFBP-3 secretion, MCF-7 breast cancer cells were incubated in serum-free medium in the presence of various levels of curcumin for specified time periods. Curcumin was found to decrease the secretion of IGF-1 in a dose-dependent manner with a concomitant increase of IGFBP-3. IGF-1-stimulated IGF-1R tyrosine kinase activation also was abrogated by curcumin in a dose-dependent manner. The authors conclude that the observed inhibition of cell growth and induction of apoptosis by curcumin in MCF-7 breast cancer cells might be mediated, at least in part, by its ability to down-regulate the IGF-1 axis.
Curcumin potentiates the growth inhibitory effect of paclitaxel through suppression of nuclear factor-kappa B in breast cancer American Association for Cancer Research (AACR) Meeting, April 2007
The present study was designed to investigate whether the inactivation of nuclear factor kappa B (NF-B) by curcumin would enhance the action of paclitaxel against breast cancer growth in vitro and in vivo. Paclitaxel is an effective chemotherapy treatment for breast cancer, but it has the major disadvantage of dose-limiting toxicity. Most anticancer drugs activate NF-B, which can help control cell survival, proliferation, and metastasis. It has been demonstrated that curcumin inhibits the growth of various types of cancer cells, without toxicity to normal cells. The anticancer effects of curcumin could be the result, in part, of the inactivation of NF-B, and therefore, blocking NF-B activity may augment the anticancer actions of paclitaxel. The authors first confirmed that curcumin resulted in inactivation of NF-B induced by paclitaxel. Next, MDA-MB-231 human breast cancer cells were treated with either 10 uM paclitaxel, 10 µM curcumin, 10 uM paclitaxel and 10 µM curcumin combined, or 10uM paclitaxel plus IKKβ dominant negative transfection, as a positive control (which totally inhibits NF-B activation). The combination of 10 µM curcumin with 10 uM paclitaxel was found to result in significantly greater inhibition of cell growth as well as more apoptosis, compared with curcumin or paclitaxel alone. Inactivation of NF-B by IKKβ DN augmented the anti-cancer effect of paclitaxel in much the same way as curcumin. Next, it was also found that therapy with a combination of paclitaxel and curcumin significantly reduced mammary tumor size and decreased tumor cell proliferation, increased apoptosis and decreased the expression of MMP-9 compared with either agent alone in experimental mice using MDA-MB-231 cells. The authors conclude that a curcumin-paclitaxel combination, which inactivates NF-B activity, may contribute to increased breast cancer cell growth inhibition and apoptosis.
Curcumin inhibits the growth of HER-2 overexpressing human breast cancer cells by interference with the glutathione pathway American Association for Cancer Research (AACR) Meeting, April 2007
The current study was designed to assess the effect of curcumin on cell growth, cell cycle and cell signaling parameters in SK-BR-3 epidermal growth factor-2 (HER-2) overexpressing human breast cancer cells. Curcumin, a yellow pigment derived from turmeric, is known for its antiseptic, anti-oxidant and anticarcinogenic qualities. Curcumin (10 microM) was found to cause cell growth inhibition associated with G2/M arrest, decrease in cyclin D1 levels and induction of cyclin dependent kinase (cdk) inhibitor p21. At 10 to 50 microM curcumin, inhibition of cell growth was also found to be associated with a decrease in phospho-HER-2 and total-HER-2 protein levels. At higher concentrations of 25 and 50 ÎM, curcumin induced apoptosis of as much as 80% of cells within 24 hours, with accumulation of cells in S and G2/M phases of cell cycle. Pre-treatment with an anti-oxidant glutathione was found to partially reverse the apoptosis induced by curcumin and restore HER-2 protein levels. The authors conclude that the anti-proliferative and apoptotic effects of curcumin on HER-2 overexpressing breast cancer cells result from interference with a number of cell growth regulatory pathways.
Identification of cell cycle and apoptosis related gene expression by curcumin in an in vitro model for ductal carcinoma in situ Proceedings of American Association for Cancer Research (AACR), Volume 46, 2005
The present study was designed to evaluate curcumin's effect on gene expression in a preclinical model for ductal carcinoma in situ (DCIS). The amplification or over-expression of oncogene HER-2/neu is found in up to 30% of DCIS breast cancer lesions. Previous work from the authors' laboratory demonstrated preventive action of curcumin (diferuloylmethane) due to cytostatic arrest of growth (S:G2/M phase of cell cycle), as well as induction of apoptosis in a mouse model for breast cancer. 184-B5 immortalized normal breast epithelial cells, established from reduction mammoplasty, lack anchorage-independent growth and are non-cancerous. A preclinical epithelial cell culture model for DCIS was developed with transformed 184-B5/HER cells which exhibits hyperproliferation, shorter population doubling time, higher saturation density, high anchorage independent growth and tumorigenicity. In the study, normal or transformed cells were treated for 24 hours with 0 uM or 20 uM curcumin. Exposure of curcumin to regular 184-B5 cells demonstrated no change in the expression of genes related to cell cycle or apoptosis, in other words, a non-responsive effect. On the other hand, curcumin treated 184-B5/HER cells evinced upregulation of the apoptosis-related genes BAX and TRAF1. Downregulated genes included cyclins A and B, CDC 2, 20 and 25C and BUB1. The authors conclude that curcumin exerts its anti-proliferative activity by reduction of cell cycle progression in S:G2/M and by induction of apoptosis through BAX and TRAF1 related mechanisms, effects that were not observed under identical conditions in normal cells.
Curcumin with Radiation Inhibits Survival of Human Breast Cancer and Murine Mammary Tumors Japanese Cancer Association Meeting, July 2004
The current study was designed to evaluate the ability of curcumin (a component of turmeric and curry powder) to act as an anti-cancer agent in breast cancer cells with and without radiation treatment. Five human breast cancer cells lines (MDA-MB-231, MCF-7, MDA-MB-453, BT-20, and SK-BR-3) and an immortalized noncancerous human mammary cell line (MCF-12A) were treated with 2μM or 5μM curcumin in the presence or absence of radiation (2 Gy or 4 Gy). Curcumin was found to act as a radiosensitizer in the five breast cancer cell lines, but as a radioprotector in the noncancerous cells. Curcumin alone (2μM and 5μM) completely prevented survival of MDA-MB-453 cells. Survival of MDA-MB-231, MCF-7, BT-20, and SK-BR-3 cells was observed to be significantly reduced with 5μM curcumin plus 4 Gy of radiation. In contrast, the MCF-12A cells were not affected by radiation in the presence of curcumin. Similarly, curcumin plus radiation was found to significantly reduce survival of Mca4 and Mca35 murine mammary tumor cells. Mouse studies demonstrated that intragastric and intraperitonal administration of curcumin (200mg/kg or 100mg/kg) caused an inhibition of Mca4 and Mca35 tumor growth in vivo. The authors conclude that curcumin inhibits growth and angiogenic factors that are critical for breast tumor cell proliferation and survival. Since curcumin has low toxicity to normal tissues and anti-tumor effects, it is a promising therapeutic agent for treatment of breast cancer
