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.
Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Kwanak-Gu, Seoul, Republic of Korea.
Won-Hee
WH
Lee
Joon-Seok
JS
Choi
Hyun Young
HY
Kim
Jeong-Hill
JH
Park
Byoung Duck
BD
Park
Seung Ju
SJ
Cho
Seung-Ki
SK
Lee
Young-Joon
YJ
Surh
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