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Article Publish Status: FREE
Abstract Title:

18β-Glycyrrhetinic-acid-mediated unfolded protein response induces autophagy and apoptosis in hepatocellular carcinoma.

Abstract Source:

Sci Rep. 2018 Jun 19 ;8(1):9365. Epub 2018 Jun 19. PMID: 29921924

Abstract Author(s):

Jin Chen, Zhao-Qi Zhang, Jia Song, Qiu-Meng Liu, Chao Wang, Zhao Huang, Liang Chu, Hui-Fang Liang, Bi-Xiang Zhang, Xiao-Ping Chen

Article Affiliation:

Jin Chen

Abstract:

18β-Glycyrrhetinic acid (GA) is the active ingredient of the traditional Chinese medicine, Glycyrrhrzae Radix et Rhizoma. Here, we explored the effects of GA on hepatocellular carcinoma (HCC) in vitro and in vivo and the underlying molecular mechanisms. We confirmed that GA suppressed proliferation of various HCC cell lines. Treatment of GA caused G0/G1 arrest, apoptosis and autophagy in HCC cells. GA-induced apoptosis and autophagy were mainly due to the unfolded protein response. We compared the roles of the ATF4/CHOP and IRE1α/XBP1s UPR pathways, which were both induced by GA. The ATF4/CHOPcascade induced autophagy and was indispensable for the induction of apoptosis in GA-treated HCC cells. In contrast, the IRE1α/XBP1s cascade protected HCC cells from apoptosis in vitro and in vivo induced by GA. Despite this, activation of autophagy protected HCC cells from apoptosis induced by GA. We concluded that pharmacological inhibition of autophagy or IRE1α may be of benefit to enhance the antitumor activity of GA.

Study Type : In Vitro Study

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