机构：[1]Department of Pharmacy, 159411The Third People's Hospital of Chengdu, Chengdu, Sichuan, People's Republic of China.[2]Wuya College of Innovation, 58575Shenyang Pharmaceutical University, Shenyang, Liaoning, People's Republic of China.[3]Department of Chemistry and Life Science, School of Advanced Engineering, Kogakuin University, Hachioji, Tokyo, Japan.[4]Nippi Research Institute of Biomatrix, Toride, Ibaraki, Japan.[5]Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, 58575Shenyang Pharmaceutical University, Shenyang, Liaoning, People's Republic of China.
The mechanism of cytotoxicity of silibinin on two human hepatocellular carcinoma (HCC) cell lines, HepG2 (p53 wild-type) and Hep3B cells (p53 null), is examined in relation with the induction of autophagy and phosphorylation of AMP-activated protein kinase (p-AMPK).Levels of apoptosis in relation to the levels of autophagy and those of glycolysis-related proteins, glucose transporter 1/4 (Glut1/4) and hexokinase-II (HK2), in HepG2 and Hep3B cells were examined.Silibinin-induced apoptosis was incomplete for HCC cell death in that up-regulated autophagy and/or reduced level of glycolysis, which are induced by silibinin treatment, antagonized silibinin-induced apoptosis. Inhibition of autophagy with 3-methyl adenine (3MA) or blocking of AMP-activated protein kinase (AMPK) activation with Compound C (CC) enhanced silibinin-induced apoptosis. The results confirm that AMPK involved in autophagy as well as in glycolysis remaining with silibinin is responsible for attenuation of silibinin-induced apoptosis. Blocking of AMPK or autophagy contributes to the enhancement of silibinin's cytotoxicity to HepG2 and Hep3B cells.This study shows that incomplete apoptosis of HCC by silibinin treatment becomes complete by repression of autophagy and/or glycolysis.
基金：
National Natural
Science Foundation of China [No. 81703528 and No.
81803603].
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2021]版：
大类|4 区医学
小类|4 区毒理学
最新[2023]版：
大类|4 区医学
小类|4 区毒理学
第一作者：
第一作者机构：[1]Department of Pharmacy, 159411The Third People's Hospital of Chengdu, Chengdu, Sichuan, People's Republic of China.[2]Wuya College of Innovation, 58575Shenyang Pharmaceutical University, Shenyang, Liaoning, People's Republic of China.
通讯作者：
通讯机构：[2]Wuya College of Innovation, 58575Shenyang Pharmaceutical University, Shenyang, Liaoning, People's Republic of China.[5]Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, 58575Shenyang Pharmaceutical University, Shenyang, Liaoning, People's Republic of China.[*1]Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, People’s Republic of China.
推荐引用方式(GB/T 7714)：
Yang J,Sun Y,Xu F,et al.Autophagy and glycolysis independently attenuate silibinin-induced apoptosis in human hepatocarcinoma HepG2 and Hep3B cells.[J].Human & experimental toxicology.2021,9603271211017609.doi:10.1177/09603271211017609.
APA：
Yang J,Sun Y,Xu F,Liu W,Hayashi T...&Ikejima T.(2021).Autophagy and glycolysis independently attenuate silibinin-induced apoptosis in human hepatocarcinoma HepG2 and Hep3B cells..Human & experimental toxicology,,
MLA：
Yang J,et al."Autophagy and glycolysis independently attenuate silibinin-induced apoptosis in human hepatocarcinoma HepG2 and Hep3B cells.".Human & experimental toxicology .(2021):9603271211017609
