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December 15, 2009
Curcumin and bioperine target breast cancer stem cells
An article published online on November 7, 2009 in the journal Breast Cancer Research and Treatment reveals the discovery by scientists at the University of Michigan Comprehensive Cancer Center that curcumin, a compound derived from the spice turmeric, and piperine from black pepper help inhibit the growth of stem cells that fuel breast cancer.
Stem cells are unspecialized cells that can develop into any type of cell in a particular organ. In their introduction to the article, University of Michigan Medical School clinical lecturer Madhuri Kakarala, MD, PhD, RD and colleagues explain that "The cancer stem cell hypothesis asserts that malignancies arise in tissue stem and/or progenitor cells through the dysregulation or acquisition of self-renewal." According to this hypothesis, the recurrence of cancer after chemotherapy is due to the drugs' ineffectiveness against cancer stem cells. Accordingly, eliminating cancer stem cells and reducing the amount of normal stem cells could decrease cancer risk.
The researchers compared the effects of varying concentrations of curcumin and piperine, alone and in combination, to a control substance administered to cultured breast epithelial cells. The amounts of curcumin and piperine employed were the equivalent of approximately 20 times the potency of what could be consumed through one's diet. They found a reduction in markers for breast stem cells in cultures treated with the lowest concentration of curcumin, and complete inhibition at twice that concentration. Piperine also demonstrated an inhibitory property, although the effects were not as pronounced as those elicited by curcumin. However, the addition of piperine to curcumin resulted in a reduction in stem cells that was greater than either agent alone, while having no effect on normal cell development or viability. “This shows that these compounds are not toxic to normal breast tissue,” Dr Kakarala remarked.
The report is the first to conclude that curcumin and bioperine could help prevent cancer by targeting stem cells. This mechanism has the potential to prevent estrogen-sensitive tumors as well as more aggressive non-estrogen dependent cancers.
“If we can limit the number of stem cells, we can limit the number of cells with potential to form tumors,” Dr Kakarala noted. “Women at high risk of breast cancer right now can choose to take the drugs tamoxifen or raloxifene for prevention, but most women won’t take these drugs because there is too much toxicity. The concept that dietary compounds can help is attractive, and curcumin and piperine appear to have very low toxicity.”
Curcumin has a number of biological effects in the body. However, one of the most important functions is curcumin's ability to inhibit growth signals emitted by tumor cells that elicit angiogenesis (growth and development of new blood vessels into the tumor).
Curcumin inhibits the epidermal growth factor receptor and is up to 90% effective in a dose-dependent manner. It is important to note that while curcumin has been shown to be up to 90% effective in inhibiting the expression of the epidermal growth factor receptor on cancer cell membranes, this does not mean it will be effective in 90% of cancer patients or reduce tumor volume by 90%. However, because two-thirds of all cancers overexpress the epidermal growth factor receptor and such overexpression frequently fuels the metastatic spread of the cancer throughout the body, suppression of this receptor is desirable.
Other anticancer mechanisms of curcumin include:
- Inhibition of the induction of basic fibroblast growth factor (bFGF), which is both a potent growth signal (mitogen) for many cancers and an important signaling factor in angiogenesis (Arbiser et al. 1998).
- Antioxidant activity. In vitro it has been shown to be stronger than vitamin E in prevention of lipid peroxidation (Sharma 1976; Toda et al. 1985).
- Inhibition of the expression of COX-2 (cyclooxygenase 2), the enzyme involved in the production of prostaglandin E2 (PGE-2), a tumor-promoting hormone-like agent (Zhang et al. 1999).
- Inhibition of a transcription factor in cancer cells known as nuclear factor-kappa B (NF-KB). Many cancers overexpress NF-KB and use this as a growth vehicle to escape regulatory control (Bierhaus et al. 1997; Plummer et al. 1999).
- Increased expression of nuclear p53 protein in human basal cell carcinomas, hepatomas, and leukemia cell lines. This increases apoptosis (cell death) (Jee et al. 1998).
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