Potentiation of etoposide-induced apoptosis in HeLa cells by co-treatment with KG-135, a quality-controlled standardized ginsenoside formulation.
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 G1 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-phosphatidylinositol-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.
Lee
Won-Hee
WH
Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Kwanak-Gu, Seoul, Republic of Korea.
Choi
Joon-Seok
JS
Kim
Hyun Young
HY
Park
Jeong-Hill
JH
Park
Byoung Duck
BD
Cho
Seung Ju
SJ
Lee
Seung-Ki
SK
Surh
Young-Joon
YJ
D000730:Androstadienes / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D004357:Drug Synergism; D005047:Etoposide / Q000494:pharmacology*; D005260:Female; D036145:Ginsenosides / Q000494:pharmacology* / Q000627:therapeutic use; D006367:HeLa Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007723:Korea; D008113:Liver Neoplasms / Q000188:drug therapy / Q000473:pathology; D008518:Medicine, East Asian Traditional; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D009183:Mycotoxins / Q000494:pharmacology; D010768:Phosphoserine / Q000378:metabolism; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000473:pathology; D000077191:Wortmannin; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
D000730:Androstadienes; D036145:Ginsenosides; D009183:Mycotoxins; D051028:bcl-2-Associated X Protein; D010768:Phosphoserine; C004564:panaxadiol; D005047:Etoposide; D000077191:Wortmannin