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Ginsenoside Rh2 induces Bcl‐2 family proteins‐mediated apoptosis in vitro and in xenografts in vivo models
Author(s) -
Choi Sunga,
Oh JunYoung,
Kim SooJin
Publication year - 2011
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.22932
Subject(s) - apoptosis , in vivo , programmed cell death , in vitro , cancer research , biology , bcl 2 associated x protein , intrinsic apoptosis , pharmacology , chemistry , caspase , caspase 3 , biochemistry , microbiology and biotechnology
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. J. Cell. Biochem. 112: 330–340, 2011. © 2010 Wiley‐Liss, Inc.