USC Study On Soy's Anti-Cancer Effects

Genistein, a component of soy, switches off cell stress response

LOS ANGELES, Mar. 4 -- Scientists have long proposed that diets high in soy may contribute to the lower incidence of certain cancers seen in Asian countries. Now, a University of Southern California/Norris study of genistein, an active component of soy products, provides one explanation of how soy could act to protect cells against cancer.

"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 Lee, Ph.D., holder of the Freeman Cosmetic Chair, professor of biochemistry and molecular biology at the USC School of Medicine and the associate director of basic research at the Norris Comprehensive Cancer Center.

In an article appearing in the March 4 Journal of the National Cancer Institute, 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. In hard times, cells turn on these so-called stress response genes to protect the body. But 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 has showed, for the first time, how genistein is able to directly suppress the mammalian stress response," says Lee, who has investigated the stress response for nearly two decades. Working with graduate research assistant Yanhong Zhou, 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," Lee says. "But we won't know whether genistein will work as an effective anti-cancer agent in people until more research is done."

Many epidemiological 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 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 at 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.

Many have looked to genistein, a bitter-tasting component of soy, to help explain soy's putative protective effects. Genistein is a natural plant estrogen with antioxidant properties. In test tube studies, the compound has been shown to halt cell growth and angiogenesis (the development of new blood vessels that tumors require for continued growth.) 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. Lee believes that genistein could act upon a number of different cellular pathways in the body, its action on the stress response being 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 an enzyme (tyrosine kinase) important in cell growth and differentiation. In earlier studies, Lee had 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," Lee says.

To receive a copy of the article, please call JNCI, at 301-496-6975. To set up an interview with Dr. Lee, please call Eva Emerson at USC Health Sciences Campus, 213-342-2830.