Life Extension Magazine October 2008
New Scientific Options for Preventing Breast Cancer
Research Update on Compounds to Incorporate Into Your Breast Health Program
By Laurie Barclay, MD
Pomegranate’s Promising Anticancer Effects
Pomegranate is an exotic fruit containing juicy, ruby-red seeds. Like green tea, the pomegranate is rich in beneficial polyphenols or flavonoids. Although it has long been valued as a medicinal plant, there have been seven times as many published studies regarding pomegranate in the past seven years as in all the preceding years.42
In addition to having anti-inflammatory effects, the juice, peel, and oil also have demonstrated anticancer activities, including interference with tumor cell growth and reproduction, cell cycle control, tumor invasion, and new blood vessel growth (angiogenesis).3,42,43
“The anti-tumor properties of the pomegranate fruit are due to the additive or synergistic effects of most of the different compounds/nutrients in the fruit,” James Kumi-Diaka, PhD, an associate professor of biological sciences at Florida Atlantic University in Davie, tells Life Extension. “Extracts of pomegranate have potential antiproliferative [anti-growth] effects on tumors including human breast cancer cell lines. Research data in our own laboratory and from elsewhere indicate that the flavonoids including phenolic acids and the pericarps’ [seed covering] tannins in pomegranate oil, all have cancer chemopreventive properties.”
Dr. Kumi-Diaka’s laboratory is studying a cell culture of human breast cancer cells known as the MCF-7 line.44 In these cells, pomegranate affects a signaling pathway involved in controlling cell division. Ultimately, pomegranate extract inhibits cancer cell growth by bringing about apoptosis, or genetically controlled cell death, which “literally means forcing the cells to ‘commit suicide,’” Dr. Kumi-Diaka says.
In a similarly promising study, purified pomegranate extract and pomegranate seed oil each reduced tumors in mouse mammary gland culture by a dramatic 87%.45
Most encouraging for the potential use of pomegranate in breast cancer is that the range of doses that inhibit growth and reproduction of tumor cells has no significant harmful effect on healthy, non-cancerous human breast cells, according to Dr. Kumi-Diaka. This observation in the MCF-7 breast cancer line has been confirmed in preliminary experiments in mice.
“I sure would recommend daily consumption of pomegranates in the form of juice drinks, beverages and/or the whole fruit,” Dr. Kumi-Diaka says. “I believe one medium size fruit, or 8-10 oz fluid a day, will be beneficial to health. It is established that the nutritional and pharmacological properties and health benefits of pomegranate are not limited to chemoprevention.”
Dr. Kumi-Diaka further suggests additional research to differentiate the impact of individual compounds in the fruit on its health benefits and anticancer activity, which may allow the design of more effective therapeutic supplements.
Curcumin’s Benefits For Breast Health
A healthy dose of curry powder may do more than add spice to your life, recent research shows. Widely used in Eastern cuisine to flavor most foods, curry powder contains the turmeric spice, rich in a healthful extract known as curcumin.
This compound has recently been shown to have a variety of health benefits including a potential role in breast cancer prevention and treatment, as is evident from its inhibition of growth in the MCF-7 breast cancer cell line4 as well as in other cell lines.46 As with other phytochemicals in the foods discussed earlier, one of the primary mechanisms of action of curcumin appears to be its effect on inducing apoptosis.46,47
Adding to the potential therapeutic benefits of curcumin are powerful anti-inflammatory effects48 as well as mechanisms that may prevent breast tumors from escaping detection by the immune system.49 Curcumin also shows benefits in inhibiting metastasis, or tumor spread.50,51 Further, in a mouse model of breast cancer, 68% of animals that received curcumin showed no or very few lung metastases, but only 17% of untreated animals were so fortunate.51
Even more promising is that in cell lines, curcumin appears to be effective against breast cancer cells that are genetically resistant to traditional chemotherapy52 and against both estrogen-positive and -negative breast cancer cells.53
About one-quarter of human breast cancers are positive for a distinctive marker known as human epidermal growth factor receptor 2 (HER2+). These tumors are more aggressive, growing faster and spreading more quickly than tumors that are not HER2+.
“Curcumin has been shown to down-regulate HER2 expression, thus mimicking Herceptin®, a drug approved for women who have HER2-positive breast cancer,” Dr. Aggarwal says. “Additionally, curcumin has been shown to sensitize the tumors to chemotherapy and gamma radiation.”
Despite these promising anticancer effects, curcumin has none of the serious toxicity associated with chemotherapy drugs. In preliminary studies in human volunteers, curcumin was not toxic even when consumed at a dosage of 12 grams per day for three months, according to Dr. Aggarwal.
The potent combination of EGCG and curcumin suppresses growth of estrogen receptor-alpha breast cancer cells in laboratory culture as well as in mice, both by stopping cell division and by reducing levels of VEGF needed for blood supply to the tumors.32 Amazingly, mice treated with both curcumin and EGCG have only half the tumor volume of untreated mice, and only one-quarter of VEGF levels in the tumors.
“These results demonstrate that the combination of EGCG and curcumin is efficacious in both [laboratory] and [mouse] models of estrogen receptor-alpha breast cancer and that regulation of [VEGF] may play a key role in this effect,” the researchers conclude.32
Soy, Estrogen, and Breast Cancer Prevention
Scientists have long wondered whether the low incidence of breast cancer in Asian women following a traditional diet5 may result from dietary factors, notably high consumption of soy and green tea. A review of several epidemiological studies suggests that high dietary intake of soy, in the amount typically consumed by Asian populations, may have protective effects against breast cancer.54
The effect of soy and tea together appears to reduce abdominal overweight, a key component of the metabolic syndrome linked not only to cardiovascular risk, but via its effects on hormones, related to breast and prostate cancers as well.55
“Our group first demonstrated that the combination of soy and tea (especially green tea) significantly prevented the growth of estrogen-dependent breast cancer in a synergistic manner,” Jin-Rong Zhou, PhD, assistant professor of surgery at Harvard Medical School and director of the Nutrition/Metabolism Laboratory at Beth Israel Deaconess Medical Center in Boston, MA, tells Life Extension. “Most animal studies have also shown the effect of soy products on breast cancer prevention. Green tea has been shown to have a breast cancer-prevention effect in both epidemiological observations and animal studies.”
Animal studies have shown that genistein, the major isoflavone in soy, helps prevent cancer by modulating genes involved in cellular reproduction and programmed cell death. Additionally, genistein interferes with estrogen- and androgen-mediated signaling pathways involved in carcinogenesis.56
Dietary intake of soy foods, particularly of the soy isoflavone genistein, during childhood and adolescence in women is associated with a lower risk of breast cancer in adulthood. A compilation of human studies also suggests that consumption of soy foods during adulthood may reduce the risk of premenopausal and postmenopausal breast cancer.57
A compound that appears particularly promising in breast cancer prevention is known as the Bowman-Birk inhibitor, a small, water-soluble protein present in soybean and in a wide variety of other seeds. Laboratory studies in tumor cells, animal models, and early clinical trials in humans have shown anticancer effects, according to a recent review.58
“FDA also approves labels claiming that consumption of at least three to four ounces of tofu or eight ounces of soymilk or soy protein may reduce the risk of coronary heart disease and breast cancer,” the review states.58
Epidemiological studies have not identified any harmful effects of dietary soy.6 “There have not been any reports of adverse effects of soy when people consume whole soy-based foods or products, so whole soy-based foods/products are considered as safe,” Dr. Zhou says.
An interesting study showed that 80% of Canadian women with breast cancer are using complementary and alternative medicine, particularly natural supplements, to help manage their disease,59 suggesting that natural food supplements shown to have activity against breast cancer would be widely embraced by these patients.
“All these compounds (vitamins, green tea, pomegranate, and curcumin) have antioxidants that exert the effects to inhibit oxidative stress related to the prevention of cancers including breast cancer,” Dr. Gu says. “However, further studies are needed in animal models and human studies [to] understand the anticancer mechanisms, [dosage] and clinical application... Based on the epidemiological studies, I would recommend consumption of these compounds, especially green tea.”
Many of the compounds discussed above, which have been shown to have benefits that could protect breast health, may act together in ways not yet fully explored. In Dr. Kumi-Diaka’s experiments with the MCF-7 breast cancer line, for example, pomegranate extract and genistein from soy each inhibit the growth of breast cancer cells by inducing apoptosis, but combination treatment is more effective than single treatments.
“Researchers are giving more efforts to investigate the potential synergistic effect of certain dietary bioactive components combination on breast cancer prevention,” Dr. Zhou says. “Some animal studies have shown that curcumin and the green tea polyphenol EGCG may have potent anti-breast cancer activity.”
Dietary compounds potentially useful in breast cancer prevention may share various mechanisms of action, including preventing DNA damage, inhibiting growth and reproduction of cancer cells, promoting cancer cell apoptosis, inhibiting blood vessel formation, and reducing inflammation.
Some of these polyphenols may be better at some of these mechanisms than others. For example, one laboratory study of breast cancer cells shows that genistein in soy actively blocks VEGF needed for new blood vessel growth to the tumor, whereas curcumin does not except at much higher concentrations.60 Using these foods together may therefore offer a multifaceted approach.
“I would feel comfortable to recommend increased consumption of whole soy-based foods or products,” Dr. Zhou says. “Especially I’d recommend soy consumption with green tea, not only because our studies showed a synergistic effect on breast cancer prevention in mice, but also because these two items are commonly consumed in Asian women, who have significantly reduced breast cancer risk.… I do recommend increasing consumption of a variety of fruits and vegetables, together with soy and green tea consumption.”
Although most experts consulted by Life Extension recommend additional studies to define mechanisms of action and to optimize dosages of individual nutrients thought to be of value in promoting breast health, they agree that the long history of safe usage as foods and in traditional medication argues for their safety as supplements.
“Vitamin D, green tea, pomegranate, and curcumin have been consumed by man for centuries and thus their side effects are minimal—that is the most attractive part of this,” Dr. Aggarwal concludes. “More clinical trials need to be done to determine the dose necessary for the treatment of cancer either alone or in combination with ongoing therapy.”
If you have any questions on the scientific content of this article, please call a Life Extension Health Advisor at 1-800-226-2370
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