AUTHOR=Fan Lu , Xiao Qingling , Chen Yanyan , Chen Gang , Duan Jinao , Tao Weiwei 

TITLE=Pekinenin E Inhibits the Growth of Hepatocellular Carcinoma by Promoting Endoplasmic Reticulum Stress Mediated Cell Death

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 8 - 2017

YEAR=2017

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2017.00424

DOI=10.3389/fphar.2017.00424

ISSN=1663-9812

ABSTRACT=Hepatocellular carcinoma (HCC) is a malignant primary liver cancer with poor prognosis. In the present study, we report that Pekinenin E (PE), a casbane diterpenoid derived from the roots of Euphorbia pekinensis, has a strong anti-tumor activity against human hepatocellular carcinoma cells both in vitro and in vivo. PE suppressed the growth of human hepatocellular carcinoma cells Hep G2 and SMMC-7721. In addition, PE-mediated ER stress caused increasing expressions of CHOP, leading to apoptosis in hepatocellular carcinoma cells both in vitro and in vivo. Inhibition of ER stress with CHOP siRNA or 4-Phenyl-butyric acid (4-PBA) partially reversed PE-induced cell death. Furthermore, PE induced S cell cycle arrest, which could also be partially reversed by CHOP knockdown. In all, these findings suggest that PE causes ER stress-associated cell death and cell cycle arrest, and it may serve as a potent agent for curing human hepatocellular carcinoma.