title: Polyphyllin VII induces apoptosis in HepG2 cells through ROS-mediated mitochondrial dysfunction and MAPK pathways.
abstract: BACKGROUND
  Paris 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.
  
  
  METHODS
  Cellular 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.
  
  
  RESULTS
  PP7 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.
  
  
  CONCLUSIONS
  These 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.
authors: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, N22-7038, Avenida da Universidade, Taipa, Macao, 999078, China.
authors: Chao
authors: C
authors: Zhang
authors: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, N22-7038, Avenida da Universidade, Taipa, Macao, 999078, China.
authors: Xuejing
authors: X
authors: Jia
authors: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, N22-7038, Avenida da Universidade, Taipa, Macao, 999078, China.
authors: Jiaolin
authors: J
authors: Bao
authors: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, N22-7038, Avenida da Universidade, Taipa, Macao, 999078, China.
authors: Shenghui
authors: S
authors: Chen
authors: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, N22-7038, Avenida da Universidade, Taipa, Macao, 999078, China.
authors: Kai
authors: K
authors: Wang
authors: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, N22-7038, Avenida da Universidade, Taipa, Macao, 999078, China.
authors: Yulin
authors: Y
authors: Zhang
authors: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, N22-7038, Avenida da Universidade, Taipa, Macao, 999078, China.
authors: Peng
authors: P
authors: Li
authors: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, N22-7038, Avenida da Universidade, Taipa, Macao, 999078, China.
authors: Jian-Bo
authors: JB
authors: Wan
authors: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, N22-7038, Avenida da Universidade, Taipa, Macao, 999078, China.
authors: Huanxing
authors: H
authors: Su
authors: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, N22-7038, Avenida da Universidade, Taipa, Macao, 999078, China.
authors: Yitao
authors: Y
authors: Wang
authors: College of Pharmacy, South Central University for Nationalities, Wuhan, 430074, China.
authors: Zhinan
authors: Z
authors: Mei
authors: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, N22-7038, Avenida da Universidade, Taipa, Macao, 999078, China. chengweihe@umac.mo.
authors: Chengwei
authors: C
authors: He
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D019668:Liliaceae / Q000737:chemistry*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012503:Saponins / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004365:Drugs, Chinese Herbal; D017382:Reactive Oxygen Species; D012503:Saponins; D016159:Tumor Suppressor Protein p53; C585643:polyphyllin VII; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human