Autophagy inhibition enhances apoptosis induced by ginsenoside Rk1 in hepatocellular carcinoma cells.
Our previous study indicated that ginsenoside Rk1 has anti-tumor activity and that its mode of action in HepG2 cells treated for 48 h involves coordinated inhibition of telomerase and induction of apoptosis. In the present study, we found that Rk1 induces both G(1) phase arrest and autophagy, but not apoptosis, at an earlier stage of treatment. A 24-h incubation of HepG2cells with Rk1 induced G(1) phase arrest. Rk1-induced autophagy was documented by the conversion of microtubule associated protein light chain 3 (LC3)-I to LC3-II, an autophagosome marker, and monodansylcadaverine (MDC) incorporation into autolysosomes. Combination of Rk1 with an autophagy inhibitor, such as bafilomycin A1 or beclin 1 siRNA, enhanced the anti-tumor effect of Rk1. These results imply that autophagy functions as a survival mechanism in HepG2 cells against Rk1-induced apoptosis. Taken together, our results support the use of autophagy inhibitors in combination with Rk1 as an effective anti-cancer regimen in HepG2 cells.
Ko
Hyeonseok
H
Natural Products Research Center, Korea Institute of Science and Technology, Gangwon-do, Korea.
Kim
Young-Joo
YJ
Park
Jin-Soo
JS
Park
Jeong Hill
JH
Yang
Hyun Ok
HO
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016193:G1 Phase / Q000187:drug effects; D036145:Ginsenosides / Q000494:pharmacology*; D006801:Humans; D008113:Liver Neoplasms / Q000175:diagnosis / Q000473:pathology*; D011379:Prognosis; D013997:Time Factors
D000970:Antineoplastic Agents; D036145:Ginsenosides; C472077:ginsenoside Rk1