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Estrogen-Like Activity of Ginsenoside Rg1 Derived from Panax notoginseng

The Open Laboratory of Chirotechnology, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University (R.Y.K.C., W.-F.C., M.-S.W.), Hung Hom, Kowloon, Hong Kong, Peoples Republic of China; and School of Pharmaceutical Sciences, Peking University (A.D., D.G.), Beijing 100083, People’s Republic of China

Address all correspondence and requests for reprints to: Man-Sau Wong, Ph.D., The Open Laboratory of Chirotechnology, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, Peoples Republic of China. E-mail: . bcmswong{at}polyu.edu.hk

Abstract

Ginsenosides have demonstrated pharmacological effects in the central nervous, cardiovascular, and endocrine systems. We hypothesize that ginsenosides might mediate some of their actions by binding to the estrogen receptor, as they share many of the protective actions of estrogen in various physiological systems. The present study is aimed to determine whether ginsenoside Rg1 can act like an estrogen analog in stimulating human breast cancer cell growth as well as in the activation of estrogen response element-luciferase activity in HeLa cell. Rg1, but not its aglycone, stimulates [methyl-³H] thymidine incorporation in estrogen receptor-positive MCF-7 in a dose-dependent manner (10^-15–10^-7 M). The stimulation of MCF-7 cell proliferation by 3 x 10^-13 M Rg1 can be blocked by 10^-6 M of the estrogen antagonist ICI 182780. Moreover, Rg1 stimulates estrogen response element-luciferase reporter gene activity in HeLa cells with an optimal dose of 3 x 10^-10 M. Such stimulation can also be blocked by 10^-6 M ICI 182780. In addition, Rg1 has no effect on [methyl-³H]thymidine incorporation in estrogen receptor-negative human breast cancer cells (MDA-MB-231). Furthermore, Rg1 failed to displace the specific binding of [³H]17ß-estradiol to MCF-7 cell lysates, suggesting that no direct interaction of Rg1 with estrogen receptor is needed for its estrogenic action. Our results indicate that ginsenosides Rg1 has estrogen-like activity and should be classified as a novel class of potent phytoestrogen.

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