Potentiation of etoposide-induced apoptosis in HeLa cells by co-treatment with KG-135, a quality-controlled standardized ginsenoside formulation

Potentiation of etoposide-induced apoptosis in HeLa cells by co-treatment with KG-135, a quality-controlled standardized ginsenoside formulation
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DOI:
10.1016/j.canlet.2010.01.024
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发表时间:
2010-08-01
期刊:
影响因子:
9.7
通讯作者:
Surh, Young-Joon
Surh, Young-Joon
中科院分区:
医学1区
文献类型:
--
作者:
Lee, Won-Hee;Choi, Joon-Seok;Surh, Young-Joon

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Our previous studies demonstrated that KG-135, a quality-controlled red ginseng-specific formulation containing approximately equal amounts of three major ginsenosides (Rk1, Rg3 and Rg5), down-regulated Cl cyclin-dependent kinase in HeLa cells. In the present work, we have found that KG-135 potentates cytotoxicity of etoposide by modulating apoptotic signaling. Co-treatment of etoposide and KG-135 markedly elevated the expression and phosphorylation at the serine 15 residue of p53 as well as the cellular levels of Bax and p21(Waf1/Cip1). The increased accumulation and phosphorylation of p53 (Ser15) were attenuated by treatment of cells with wortmannin, a pan-phosphatidylinosito1-3 kinase inhibitor. Moreover, co-treatment of etoposide and KG-135 enhanced mitochondrial localization of Bax. Our results indicate that etoposide-induced apoptosis in HeLa cells can be potentiated in the presence of KG-135 through a mechanism that involves the stabilization of p53 and the stimulation of Bax- and p21-mediated apoptotic signaling pathways. These findings suggest that KG-135 represents a useful candidate adjuvant for the treatment of cancers that could potentially minimize the adverse effects of current clinical chemotherapeutics. (C) 2010 Elsevier Ireland Ltd. All rights reserved.