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

被引：31

作者：

Chen, Jin ^{[1
]}

Zhang, Zhao-qi ^{[1
]}

Song, Jia ^{[1
]}

Liu, Qiu-meng ^{[1
]}

Wang, Chao ^{[1
]}

Huang, Zhao ^{[1
]}

Chu, Liang ^{[1
]}

Liang, Hui-fang ^{[1
]}

Zhang, Bi-xiang ^{[1
]}

Chen, Xiao-ping ^{[1
]}

机构：

[1] Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Hepat Surg Ctr, Wuhan 430030, Hubei, Peoples R China

来源：

SCIENTIFIC REPORTS | 2018年 / 8卷

基金：

中国国家自然科学基金;

关键词：

ENDOPLASMIC-RETICULUM STRESS; GLYCYRRHETINIC ACID; ER STRESS; DEATH RECEPTOR; GROWTH-FACTOR; CELL FATE; MECHANISMS; MODULATION; ACTIVATION; TRIGGERS;

D O I：

10.1038/s41598-018-27142-5

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

18 beta-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 IRE1 alpha/XBP1s UPR pathways, which were both induced by GA. The ATF4/CHOP cascade induced autophagy and was indispensable for the induction of apoptosis in GA-treated HCC cells. In contrast, the IRE1 alpha/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 IRE1 alpha may be of benefit to enhance the antitumor activity of GA.

引用

页数：13

共 44 条

[1] Endoplasmic reticulum architecture: structures in flux [J].