Polyphyllin VII induces apoptosis in HepG2 cells through ROS-mediated mitochondrial dysfunction and MAPK pathways

BMC Complementary and Alternative Medicine

Research Article

Zhinan Mei¹  Jian-Bo Wan²  Huanxing Su²  Jiaolin Bao²  Xuejing Jia²  Chengwei He²  Yulin Zhang²  Kai Wang²  Chao Zhang²  Shenghui Chen²  Peng Li²  Yitao Wang² 

[1] College of Pharmacy, South Central University for Nationalities, 430074, Wuhan, China;State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, N22-7038, Avenida da Universidade, Taipa, 999078, Macao, China;

关键词: Polyphyllin VII;    Apoptosis;    MAPK pathways;    Anticancer;    HepG2 cells;   

DOI  :  10.1186/s12906-016-1036-x

 received in 2015-10-03, accepted in 2016-02-02,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundParis polyphylla is an oriental folk medicine that has anticancer activities both in vivo and in vitro. Polyphyllin VII (PP7), a pennogenyl saponin from P. polyphylla has been found to exert strong anticancer activity. However, the underlying mechanisms are poorly understood. In the present study, the anticancer effect of polyphyllin VII against human liver cancer cells and the molecular mechanisms were investigated.MethodsCellular viability was measured by MTT assay. Apoptosis, intracellular reactive oxygen species (ROS) and mitochondrial membrane potential levels were evaluated using the InCell 2000 confocal microscope. The expression levels of apoptotic-related proteins were evaluated by Western blotting.ResultsPP7 strongly inhibited the cell growth and induced apoptosis and necrosis in hepatocellular carcinoma HepG2 cells. Meanwhile, PP7 up-regulated the levels of Bax/Bcl-2, cytochrome c, the cleaved forms of caspases-3, -8, -9, and poly (ADP-ribose) polymerase in a dose- and time-dependent manner, indicating that PP7 induced apoptosis in HepG2 cells through both intrinsic and extrinsic pathways. Moreover, PP7 provoked the production of intracellular ROS and the depolarization of mitochondrial membrane potential. Further analysis showed that PP7 significantly augmented the phosphorylation of JNK, ERK and p38, the major components of mitogen-activated protein kinase (MAPK) pathways, and the expressions of tumor suppressor proteins p53 and PTEN. In addition, PP7-induced apoptosis was remarkably attenuated by MAPK inhibitors and ROS inhibitor.ConclusionsThese results demonstrated that PP7 induced apoptotic cell death in HepG2 cells through both intrinsic and extrinsic pathways by promoting the generation of mitochondrial-mediated ROS and activating MAPK and PTEN/p53 pathways.

【 授权许可】

CC BY   
© Zhang et al. 2016