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

• Main Authors: Lu Fan, Qingling Xiao, Yanyan Chen, Gang Chen, Jinao Duan, Weiwei Tao
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2017-06-01
• Series: Frontiers in Pharmacology
• Subjects: pekinenin E; hepatocarcinoma; ER stress; apoptosis; cell cycle arrest
• Online Access: http://journal.frontiersin.org/article/10.3389/fphar.2017.00424/full

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 antitumor activity against human HCC cells both in vitro and in vivo. PE suppressed the growth of human HCC cells Hep G2 and SMMC-7721. In addition, PE-mediated endoplasmic reticulum (ER) stress caused increasing expressions of C/EBP homologous protein (CHOP), leading to apoptosis in HCC cells both in vitro and in vivo. Inhibition of ER stress with CHOP small interfering RNA or 4-phenyl-butyric acid 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 HCC.