Extraction-Dependent Effects of American Ginseng (Panax quinquefolium) on Human Breast Cancer Cell Proliferation and Estrogen Receptor Activation

Abstract

Hypothesis:Ginseng root extracts and the biologically active ginsenosides have been shown to inhibit proliferation of human cancer cell lines, including breast cancer. However, there are conflicting data that suggest that ginseng extracts (GEs) may or may not have estrogenic action, which might be contraindicated in individuals with estrogen-dependent cancers. The current study was designed to address the hypothesis that the extraction method of American ginseng (Panax quinquefolium) root will dictate its ability to produce an estrogenic response using the estrogen receptor (ER)-positive MCF-7 human breast cancer cell model. Methods: MCF-7 cells were treated with a wide concentration range of either methanol-(alc-GE) or water-extracted (w-GE) ginseng root for 6 days. Cells were grown in media containing either normal or charcoal-stripped fetal calf serum to limit exposure to exogenous estrogen. Thus, an increase in MCF-7 cell proliferation by GE indicated potential estrogenicity. This was confirmed by blocking GE-induced MCF-7 cell proliferation with ER antagonists ICI 182,780 (1 nM) and 4-hydroxytamoxifen (0.1 µ µM). Furthermore, the ability of GE to bind ERα α or ERβ β and stimulate estrogen-responsive genes was examined. Results: Alc-GE, but not w-GE, was able to increase MCF-7 cell proliferation at low concentrations (5-100 µ µg/mL) when cells were maintained under low-estrogen conditions. The stimulatory effect of alc-GE on MCF-7 cell proliferation was blocked by the ER antagonists ICI 182,780 or 4-hydroxytamoxifen. At higher concentrations of GE, both extracts inhibited MCF-7 and ER-negative MDA-MB-231 cell proliferation regardless of media conditions. Binding assays demonstrated that alc-GE, but not w-GE, was able to bind ERα α and ERβ β. Alc-GE (50 µ µg/mL) also induced an approximate 2.5-fold increase in expression of the estrogenresponsive pS2 gene, as well as progesterone receptor (PgR) gene expression, whereas w-GE was without effect. Conclusion: These data indicate that low concentrations of alc-GE, but not w-GE, elicit estrogenic effects, as evidenced by increased MCF-7 cell proliferation, in a manner antagonized by ER antagonists, interactions of alc-GE with estrogen receptors, and increased expression of estrogenresponsive genes by alc-GE. Thus, discrepant results between different laboratories may be due to the type of GE being analyzed for estrogenic activity.

A Lipid-Soluble Red Ginseng Extract Inhibits the Growth of Human Lung Tumor Xenografts in Nude Mice

“…4 Ginseng has been consistently shown to inhibit tumor growth in both in vitro and in vivo tests. 5 Most investigations of ginseng's anticancer activity have focused on the inhibition of human cancer cell proliferation in vitro 6,7 and on the inhibition of tumor growth in animals bearing cancer cells in vivo. [8][9][10] In particular, aqueous extracts of ginseng as well as ginseng itself have been applied to animal and human studies in vivo.…”

Selective extraction of Cyclopia for enhanced in vitro phytoestrogenicity and benchmarking against commercial phytoestrogen extracts

“…The polar solvents, 50% methanol-distilled water or water, extracted little to no estrogenic activity. Other parameters that could affect the effectiveness of extraction are ratio of solvent to plant material [44], extraction method [46,49], and time and temperature of extraction [44,48]. A study of additional factors that could affect the extraction effectiveness of Cyclopia may be considered in future, especially an investigation of the effects of temperature in light of our results with the "cup-of-tea" extraction.…”

“…For example, extraction of yam with ethyl acetate, but not methanol or n-hexane, produced extracts with estrogenic activity [45] while in other studies methanol or ethanol extracts of ginseng root or soybean, respectively, yielded estrogenic extracts [44,46]. Less polar solvents such as acetonitrile have been suggested by some to be more effective for soybean extraction [47] while other authors present data suggesting that more polar solvents, such as methanol-water, extract more estrogenic compounds from soybean [48].…”

Evaluation of an extract of North American ginseng (Panax quinquefolius L.) in Candida albicans-infected complement-deficient mice

“…The HWEG was tested at concentrations ranging from 20 to 640 g/mL (King et al, 2006;Sung and Lee, 2008) and was compared with the known anti-Candida albicans agent fluconazole (0.25-64 g/mL). Fluconazole showed the expected minimum inhibitory concentration of 0.25-1 g/mL (data not shown).…”