Curing breast cancer and special benefits of Soy and Blueberry polyphenols

Curing breast cancer and special benefits of Soy and Blueberry polyphenols

Genistein and Blueberry polyphenols may lower the breast cancer incidence caused by tumor-initiating stem/progenitor cells

Frontier Voice of Nutrition Remarks (February 15, 2012)

Nalin Siriwardhana, PhD, interviewed Professor Rosalia C. M. Simmen, Ph.D. from the Arkansas Children’s Nutrition Center and the University of Arkansas for Medical Sciences, Little Rock, AR, USA

Breast cancer-causing stem/progenitor cells are highly resistant to anti-cancer drugs. However, an exciting finding from Prof. Rosalia Simmen’s group shows that the soy component Genistein and phenolic acids present in Blueberries may selectively block those dangerous potentially tumor-initiating cells from increasing in numbers.

Professor Rosalia C. M. Simmen, Ph.D.

Most of the current breast cancer drugs that shrink or kill breast cancer cells do not effectively kill breast cancer stem/progenitor cells that initiate tumors. Therefore, even after treatments, these breast cancer stem cells can redevelop and allow the tumor to continue to grow. In order to prevent breast cancer from recurring and to prevent further tumor formation, it is necessary for such cells to be killed or suppressed. The recent findings from laboratory studies conducted by Prof. Simmen’s group, suggest that such breast cancer stem cells can be selectively suppressed by Genistein (a popular soy isoflavone that also show estrogen-like bioactivities under certain conditions) and Blueberry polyphenols.

Nutrition Remarks interviewed Prof. Rosalia C.M. Simmen, Ph.D., at the Arkansas Children’s Nutrition Center and the University of Arkansas for Medical Sciences. Dr. Simmen is a prominent scientist who has been conducting research for the last ten years on the actions of bioactive compounds present in foods that may prevent adult breast cancer onset and progression. A simplified version of the conversation is as follows:

Question from Nutrition Remarks: What is the danger associated with cancer causing stem cells?

Answer from Dr. Simmen: Under normal conditions, breast stem/progenitor cells are important for the proper functioning of the breast mammary gland (small units that produce milk in the brest) as these cells give rise to epithelial cells that allow the mammary gland to dramatically grow during puberty/adolescence and also during pregnancy in preparation for milk production. However, under abnormal conditions, these cells may undergo mutations (permanent changes in genes) resulting in ‘damaged’ cells that grow without control. These ‘damaged’ cells are considered to give rise to cancer. Interestingly, these stem cells are found to be highly resistant to drugs that are currently used to treat breast cancer. Thus, drugs that shrink tumors may not necessarily kill stem cells that cause cancer; hence, the challenge remains for finding ways to totally eliminate these cells. .

Question: In humans, normal breast epithelial cells (epithelial cells) take some time to transform into cancer cells. How about mammary stem cells in terms of vulnerability?

Answer: Breast stem cells are the parent cells for epithelial cells. Breast stem cells under normal conditions do not rapidly divide; they sit quietly and hence, can accumulate mutations. These mutations cause damage to DNAs that code for proteins necessary for normal cell functions and normal growth process. When mutated, they rapidly give rise to daughter/progenitor cells that are also mutated and can grow unregulated, leading to cancer.

It takes a long time (as much as 20 years or greater) to develop breast cancer in the general population since many mutations have to occur. Breast cancer, similar to many types of cancer, is a multi-step process. Breast cancer is an old age disease; as we age, cells are exposed to many mutation-causing agents coming from the external environment and from stress-induced byproducts in cells. The current thinking is that mutations in stem cells and their ‘daughter/progenitor’ cells may lead to damaged epithelial cells that give rise to tumors.

Question: What is the role of estrogen on breast cancer-causing stem cells?

Answer: Exposure to excessive amounts of estrogens is a risk factor for breast cancer. Excessive estrogen exposure can cause mutations, allowing the uncontrolled growth of mutated cells. Estrogens, however, do not directly target breast stem cells due to lack of estrogen receptors in these cells. Rather, estrogens act indirectly, by influencing the growth of cells surrounding the stem cells, to support their uncontrolled growth. Estrogens may also act on mutated daughter/progenitor cells arising from stem cells to cause cancer.

Question: What are the important reasons to select Genistein and Blueberry polyphenols for your studies?

Answer: Those are major constituents of foods that we eat frequently. Genistein is a major component of soy foods. The polyphenols we used in our studies are also found in many berry fruits. In these times of rising obesity epidemic and the push for the importance of healthy eating to combat this trend, it is important to study how the foods that are readily available to the general population and which we normally eat, can affect our health.

Epidemiological studies have shown that women in Asian countries (China, Japan and Korea) who consume soy-based foods as part of their regular diets have lower incidence of breast cancer. Our studies as well as those of many others have shown that soy food intake is protective against breast cancer in rat- and mouse-based experiments and have identified genistein as one of the key bioactive components partly responsible for the mammary tumor-protective effects of soy. Similarly, in rat and mouse experiments, we and others have shown that dietary intake of whole blueberry powders can be protective against breast cancer formation. Blueberry polyphenols can inhibit the growth of breast cancer cells in culture. Given these studies and the current thinking that breast cancer initiation and progression may arise from stem cells, the next step is to link the breast cancer protective effects of these factors with their ability to inhibit growth of cancer stem cells. Our current study demonstrates this linkage.

Question: Are there any epidemiological evidences to support your promising experimental data?

Answer: There are epidemiological studies to show that intake of soy foods may prevent breast cancer and may protect against breast cancer recurrence. However, a number of clinical studies also report on the lack of effects of soy food intake on improving breast cancer outcome. More studies are definitely needed to address these conflicting results and to further understand the therapeutic potential of soy food (genistein) intake. However, I am in the opinion that the effects (or lack thereof) in the reported studies may be associated with amounts taken. Our studies show that the lower dose of genistein is more effective than the higher dose. This is also true for blueberry polyphenols. I guess this is the case of more being not necessarily good; hence, moderation is a key. It may be best to consume moderate amounts regularly. Therefore, our findings are novel given that the doses we used are easily achievable and similar to what the cells are really exposed to in vivo.

Question: Several laboratory studies (with representative breast cancer cells) suggest that the phytoestrogen genistein can potentially promote cancer cell growth. However, Dr. Hilakivi‐Clarke (from Lombardi Comprehensive Cancer Center, Washington, DC, USA) suggested that soy intake during early life may reduce breast cancer risk.

Answer: Most of the cell culture studies showing that genistein can promote cancer cell growth were performed using extremely high doses of genistein. Those doses are not achievable with regular soy food consumption or by taking genistein supplements. Indeed, our studies show positive effects at a very low dose, which is physiologically achievable and a thousand-fold less than the concentrations used in those studies. Genistein has estrogenic effects at high doses; hence, this may explain the growth promoting actions previously observed.

Our studies agree with those of Dr. Hilakivi-Clarke. Indeed, using rat models, we have previously reported that soy exposure during very early life can affect mammary tumor outcome. Also, we have similar data for whole blueberry powder intake. In an earlier study, we found that intake of blueberry powder by pregnant and lactating dams resulted in more developed mammary glands in pups. Indeed, the developing concept that exposure to specific diets during early life can influence the potential for onset of adult breast cancer is very exciting. It supports the notion that “we are what our mothers eat”.

Question: What is your next step?

Answer: There are many questions that are needed to be addressed. For example, are these effects of genistein and blueberry polyphenols that we showed in breast cancer cells in culture also true in animal models of breast cancer? It is important to show that what we observed in mammary cells in culture actually happens in vivo when we consume specific foods. Another important question relates to what other specific polyphenols present in fruits and other bioactive factors present in soy foods might show similar activities. These will expand the inventory of potential therapies that may be effective in different types of breast cancer since, as we have shown in our studies, different dietary factors have different effects on breast cancer type (estrogen receptor-positive vs. estrogen receptor-negative breast cancers).

Question: What are the other important facts that we did not discuss here?

Answer: I mentioned above the dose-dependent effects of the bioactive components in foods, hence, the necessity for moderation. I believe this is an important concept not only in experiments in the laboratory but also in how much we consume through our diets for good health. In an earlier study (2009), we found, in experiments using pregnant rats, that adding 10% whole blueberry powders to maternal diet had no demonstrable effects on the mammary gland health of progeny, whereas addition of 2.5% and 5% whole blueberry powder showed positive effects. The latter is achievable by consuming ½ to 1 cup of blueberries a day, which is not excessive.

Another important concept is that maternal health (which can be achieved through healthy eating during pregnancy) is important for the health status of progeny. This is a concept gaining support not only from our own studies but also in many studies from other laboratories. In this regard, my colleague (Dr. Frank Simmen) and I have recently published a review on this topic in the European Journal of Cancer Prevention entitled: The maternal womb: a novel target for cancer prevention in the era of the obesity pandemic?

Yet another important concept is prevention. While we may have means to improve breast cancer outcome (through diet by preventing breast cancer progression and recurrence), the major point we want to get across is why not start early by preventing mammary tumor from developing.

This news release was based on the following original scientific article published by Prof. Rosalia C. M. Simmen, Ph.D. in Carcinogenesis journal. Some general background information was acquired from PubMed and NIH sources.

Montales et al., Repression of Mammosphere Formation of Human Breast Cancer Cells by Soy Isoflavone Genistein and Blueberry Polyphenolic Acids Suggests Diet-Mediated Targeting of Cancer Stem-Like/Progenitor Cells Carcinogenesis bgr317 first published online January 4, 2012 doi:10.1093/carcin/bgr317.

Professor Rosalia C. M. Simmen, Ph.D, is currently Professor in the Department of Physiology and Biophysics at the University of Arkansas for Medical Sciences (UAMS) and Senior Investigator in Developmental Biology at the Arkansas Children’s Nutrition Center. Her research is focused on women’s health, with emphasis on the biology and pathophysiology of the uterus and the mammary gland. She is also a faculty member of the Winthrop Rockefeller Cancer Institute at UAMS.

More about Prof. Rosalia and work

http://www.uams.edu/physiology/faculty/rsimmen.htm

http://achri.archildrens.org/researchers/SimmenR.htm

http://acnc.uamsweb.com/?page_id=991

Prof. Simmen acknowledges support for this research by the following funding agencies: USDA-ARS (CRIS 6251-5100002-06S), Arkansas Children’s Nutrition Center; Department of Defense Breast Cancer Research Program; and the Arkansas Children’s Hospital Children’s University Medical Group.

Individuals who contributed significantly to these findings include postdoctoral fellow Dr. Maria Theresa Montales, M.D., and senior PhD student Omar Rahal.

Written by Nalin Siriwardhana, Ph.D. and Suhanki Rajapaksa MBBS.

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