The
cancer chemoprevention effects of ginseng
saponins have been demonstrated against a variety of experimental
tumors; however, their molecular mechanisms in vitro and in in vivo models are not well studied. This study was undertaken to gain insights into the molecular mechanisms of
ginsenoside Rh2 (Rh2)-induced cell death in human
breast cancer cell lines as well as in in vivo xenografts. Rh2 treatment significantly inhibited viability of both MCF-7 and MDA-MB-231 human breast cells in a concentration-dependent manner, which correlated with mitochondria-mediated apoptosis. Rh2-induced apoptosis was accompanied by the down-regulation of antiapoptotic
proteins Bcl-2, Bcl-xL, and Mcl-1. It also caused induction of the proapoptotic members Bak, Bax, and Bim leading to mitochondrial translocation of Bax and activation of
caspases. Moreover, Rh2-induced apoptosis was partially, yet significantly protected by transient transfection of MCF-7 cells with Bax- and Bak-targeted siRNAs. Oral gavage of 5 mg Rh2/kg of mouse (three times a week) significantly caused apoptosis of MDA-MB-231 xenografts. An increase in Bax and Bak and a decrease in Bcl-2 and Bcl-xL transcript levels, in accordance with their
protein expression, were observed in
tumor tissue.
Tumors from Rh2-treated mice exhibited a markedly higher count of apoptotic bodies and reduced proliferation index compared with control
tumors. Our data suggest that Rh2 used in
traditional oriental medicine for the treatment of various ailments, may be an attractive agent for the treatment and/or prevention of human breast
cancers.