Autophagy inhibition enhances ginsenoside Rk1-induced cytotoxicity and G1 phase arrest in hepatocellular carcinoma cells

Title
Autophagy inhibition enhances ginsenoside Rk1-induced cytotoxicity and G1 phase arrest in hepatocellular carcinoma cells
Authors
고현석김영주양현옥
Keywords
Rk1; autophagy; G1 phase arrest; HCC
Issue Date
2009-04
Publisher
American Association for Cancer Research (AACR)
Abstract
Our previous study represented that the biological activity of ginsenoside Rk1 against hepatocellular carcinoma HepG2 cell growth and the mechanism underlying the anti-tumor activity of Rk1 involved coordination between inhibition of telomerase activity and induction of apoptosis. However, the effects of Rk1 in the early stage for HepG2 cells remain unclear. Here, we demonstrate that Rk1 induces both autophagy and G1 phase arrest in early stage. As our previous report represent, when Rk1 was treated with 100uM for 48 h, HepG2 cells underwent apoptosis. However, when it was treated for 24 h, HepG2 cells underwent autophagy but not apoptosis and G1 phase arrest through decreasing of phospho-Rb and CDK4 expression level, which is correlated with G1 phase. Interestingly, inhibition of autophagy by bafilomycin A1 sensitized HepG2 cells to Rk1 by inducing apoptosis within 24hr. Additionally, the silencing Beclin 1 with small interfering RNA increased the number of Rk1-induced apoptotic cells within 24 h. Therefore, we speculate that autophagy protects HepG2 cells from Rk1-induced apoptosis in early stage, however, when HepG2 cells are exposed by Rk1 for a long time, the cells finally undergo apoptosis. We identify that Rk1 induced the dual effects of autophagy and G1 phase arrest in early stage, and inhibition of autophagy enhanced Rk1-induced apoptosis. These results imply an autophagy functions as a survival mechanism in HepG2 cells against Rk1-induced apoptosis. Taken together, this provided evidence that a rationale for the use of autophagy inhibitor in combination with Rk1 in HepG2 cells.
URI
http://pubs.kist.re.kr/handle/201004/36381
Appears in Collections:
KIST Publication > Conference Paper
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