Scientists have long proposed that diets high in soy may contribute to the lower incidence of certain cancers in Asian countries. Now, a University of Southern California/Norris Comprehensive Cancer Center study of genistein, an active component of soy products, provides one explanation of how soy could protect cells against cancer.
Genistein and the Stress Response
“The study links a natural component of our diet to the control of the cellular stress response, which plays an important role in many kinds of cancer and cancer drug resistance,” says Amy S. Lee, phd. The holder of the Freeman Cosmetic Chair and professor of biochemistry and molecular biology at the USC School of Medicine, Dr. Lee is also associate director of basic research at Norris Comprehensive Cancer Center.
In an article published in the March 4th Journal of the National Cancer Institute, Dr. Lee reports how genistein turns off the defense mechanism that cells use to survive under stressful conditions, such as starvation, malnutrition, lack of oxygen, infection, extreme heat—and cancer. Under certain conditions, cells activate stress-response genes to protect the body. However, in cancer cells, scientists think stress proteins may inadvertently worsen disease, helping tumor cells to elude the body’s immune system and resist chemotherapy and other cancer treatments.
“Our group demonstrated, for the first time, how genistein is able to directly suppress the mammalian stress response,” says Dr. Lee, who has investigated the stress response for nearly 2 decades. Working with graduate research assistant Yanhong Zhou, Dr. Lee found that, in cell cultures, genistein blocks the activity of a cellular protein, a transcription-activating factor that switches on the stress-response genes.
“It’s clear that most cancer cells make a lot more stress proteins than normal cells do, and genistein prevents that from happening. In animal models, suppression of the stress response has been shown to suppress cancer growth,” Dr. Lee says. “But we won’t know whether genistein will work as an effective anti-cancer agent in people until more research is done.”
Diet vs Genetics
Many epidemiologic studies have found that Asians living in Asia have a fairly low risk of developing cancers of the prostate, breast, and colon. Yet, Asians who immigrate to America typically see their risk go up. Researchers, looking for an environmental cause to explain this, have focused on diet, and most intensely on soy, since Asians consume 20 to 50 times more soy per capita than do Americans. Soy intake falls in Asian-Americans, according to a 1996 report from USC/Norris researchers led by Malcolm Pike, professor and chair of preventive medicine in the School of Medicine. In that study, the team found that Asian-American women who ate the most tofu had a lower risk of developing breast cancer.
More Study Needed
Many have looked to genistein, a bitter-tasting component of soy, to help explain the putative protective effects of soy. Genistein is a natural plant estrogen with antioxidant properties. In test tube studies, the compound has been shown to halt cell growth and angiogenesis. Another team gave genistein to female rats as newborns and later exposed the rats to a tumor-inducing carcinogen. The treated rats developed mammary cancer much later than non-treated controls. Some researchers have theorized that genistein’s protective effect in breast cancer could come from its ability to block estrogen receptors. Dr. Lee believes that genistein could act on a number of different cellular pathways in the body, and that its action on the stress response is just one way that the compound influences cancer growth.
For the last decade, scientists have used genistein as a biochemical tool because of its ability to block tyrosine kinase, important in cell growth and differentiation. In earlier studies, Dr. Lee found that it could also block the stress response. “But until now the targets of genistein action have not been well understood. Our work provides a molecular mechanism for genistein action at the DNA level. We predict that other genes important in cancer progression may also be targets of genistein. I suspect that this finding will lead to more exciting discoveries about the anti-cancer effects of soy,” Dr. Lee says.
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