Ginseng and Breast Cancer

Sharon K. Krueger, Ph.D.
Research Associate
Department of Environmental and Molecular Toxicology
David E. Williams, Ph.D.
Professor of Environmental and Molecular Toxicology
LPI Principal Investigator

Summary: A crude fraction of American ginseng was found to inhibit the growth of human breast cancer cells in culture. At high doses, this ginseng fraction was also able to kill cultured human breast cancer cells. Future experiments will investigate the bioavailability and anticancer effect of this fraction in animals or humans.

Breast cancer is the most commonly diagnosed cancer in women of developed countries—as many as one in eight North American women can expect to develop breast cancer during their lifetime. Many experts believe that breast cancer results from exposure to endogenous or exogenous hormones that alter estrogen metabolism, since one risk factor is a greater cumulative exposure to 17b-estradiol, a potent steroid hormone produced in ovaries that induces estrogenic activity. A significant percentage of breast cancers are hormonally dependent, i.e. estrogen stimulates their growth. Estradiol binds to the estrogen receptor of cells; this complex in turn binds to and modulates the expression of estrogen-responsive genes. Women diagnosed with hormonally responsive breast cancer are routinely treated with antiestrogenic compounds, such as tamoxifen, which block the estrogen receptor and prevent binding of estradiol.

Many plants, including common foods and herbs, contain phytoestrogens, which are naturally occurring compounds that are structurally or functionally similar to estradiol. Phytoestrogens can affect the metabolism of estradiol or bind directly to the estrogen receptor, thereby exerting either estrogenic or antiestrogenic effects. The strongest evidence that dietary intake of phytoestrogens lessens the likelihood of developing hormonally regulated cancers is provided by epidemiological studies that demonstrate a link between a high intake of soybean products, which contain the phytoestrogens genistein and daidzein, and a lower incidence of breast, endometrial, prostate, and colon cancers. Among Asian populations that consume a traditional soybean-rich diet, the incidence of these cancers is low. However, among Asian populations that adopt a typical Western, soybean-poor diet, the risk of hormonally regulated cancers rises. Thus, these compounds may modulate the proliferation of breast cells and the development of cancer.

Ginsenosides are phytoestrogens found in ginseng that may be expected to have effects similar to those of soy phytoestrogens. There are two species of ginseng readily available to consumers in the United States. The root of Korean ginseng (Panax ginseng) has been used in Chinese medicine for thousands of years, while the use of American ginseng (Panax quinquefolius) can be traced to native Americans in the U.S. and Canada. The pharmaceutical properties of ginseng are attributed to an array of more than 30 ginsenosides that share a common steroid-like chemical structure. Some ginsenosides are common to both species, although present in different relative quantities, while others are unique to one species or the other. Although structurally similar, studies have demonstrated markedly different biochemical effects of different ginsenosides.

Cell culture studies have demonstrated that certain ginsenosides have anticancer effects, including dose-dependent inhibition of cell growth, tumor cell toxicity, reverse transformation of tumor cells (restoration of normal cell appearance and properties), and inhibition of tumor cell invasion (a measure of metastatic capacity). However, not all ginsenosides have anticancer properties.

Since ginsenosides have a steroidal structure, we think that they may have their most profound anticancer effects on hormonally regulated cancers, such as breast cancer. Thanks to pilot project funding from the Linus Pauling Institute, we designed and conducted some experiments to determine 1) whether crude extracts or pure ginsenosides isolated from American ginseng are estrogenic, 2) whether ginsenosides bind to the estrogen receptor on cells, and 3) whether ginsenosides combined with other compounds have anticancer effects. We tested crude extracts and purified ginsenosides isolated from American ginseng using a breast cancer cell line developed 27 years ago by the late Dr. Herbert Soule of the Michigan Cancer Foundation. These cells, derived from a patient with metastatic breast cancer, have been widely used as an in vitro model for the study of hormone responsive breast cancer. The estrogen receptors on these cells bind estrogenic compounds, which induces the synthesis of the progesterone receptor and certain "marker" proteins that identify cancer cells—features that are of clinical relevance in determining the therapeutic course of action among women diagnosed with breast cancer. These breast cancer cells grow faster in the presence of exogenous estrogens, whereas antiestrogens like tamoxifen inhibit their replication.

We evaluated the anticancer effect of a range of ginseng compounds in varying doses by adding these compounds to the media in which the breast cancer cells were grown. When the cancer cells were exposed to the ginsenosides in a six-day assay, none of the ginsenosides enhanced the growth of the cells, but the crude fraction we have designated as PQe not only inhibited proliferation of the cancer cells at all doses but actually caused significant tumor cell death when administered at high doses. In a ten-day assay, one ginsenoside (Rc) enhanced the proliferation of the cancer cells, but all other ginsenosides were either neutral or inhibitory. Again, PQe had the greatest inhibitory effect: after 10 days, the number of cancer cells had been reduced by 98% compared to control cell cultures.

Our studies led us to conclude that the ginsenosides are not estrogenic. Whereas treatment of the breast cancer cells with the steroid hormone estradiol greatly enhanced their proliferation, cells treated with both estradiol and ginsenosides exhibited growth inhibition, which suggests that ginsenosides affect the estrogen receptor. Our future experiments will test the ability of ginsenosides to compete with the binding of estradiol to estrogen receptors. We also plan to examine the effect of ginsenosides on protein levels of genes important in breast cancer. Then we want to discover why the crude PQe fraction kills breast cancer cells, while other ginsenosides are much less effective. It will also be important to assess the relative bioavailability of different ginsenosides in order to determine how much of an oral dose actually enters the bloodstream.By understanding these mechanisms and investigating the promising compounds in animal models, we may then be ready to evaluate the effectiveness of ginsenosides in preventing or treating human breast cancer.

Last updated May, 2000

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