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BMC Complementary Medicine and Therapies
Published in: BMC Complementary Medicine and Therapies 1/2016

Open Access 01-12-2015 | Research article

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

Authors: Chao Zhang, Xuejing Jia, Jiaolin Bao, Shenghui Chen, Kai Wang, Yulin Zhang, Peng Li, Jian-Bo Wan, Huanxing Su, Yitao Wang, Zhinan Mei, Chengwei He

Published in: BMC Complementary Medicine and Therapies | Issue 1/2016

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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.
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Metadata
Title
Polyphyllin VII induces apoptosis in HepG2 cells through ROS-mediated mitochondrial dysfunction and MAPK pathways
Authors
Chao Zhang
Xuejing Jia
Jiaolin Bao
Shenghui Chen
Kai Wang
Yulin Zhang
Peng Li
Jian-Bo Wan
Huanxing Su
Yitao Wang
Zhinan Mei
Chengwei He
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2016
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-016-1036-x

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