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Polyphyllin VII induces apoptosis in HepG2 cells through ROS-mediated mitochondrial dysfunction and MAPK pathways
Zhang C.1; Jia X.1; Bao J.1; Chen S.1; Wang K.1; Zhang Y.1; Li P.1; Wan J.-B.1; Su H.1; Wang Y.1; Mei Z.2; He C.1
2016
Source PublicationBMC complementary and alternative medicine
Volume16Pages:58
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.

KeywordPolyphyllin Vii Apoptosis Mapk Pathways Anticancer Hepg2 Cells
DOIhttp://doi.org/10.1186/s12906-016-1036-x
URLView the original
Indexed BySCI
Language英语
WOS Research AreaIntegrative & Complementary Medicine
WOS SubjectIntegrative & Complementary Medicine
WOS IDWOS:000369606200001
The Source to ArticleScopus
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Cited Times [WOS]:29   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorHe C.
Affiliation1.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
2.College of Pharmacy, South Central University for Nationalities, Wuhan, 430074, China
First Author AffilicationInstitute of Chinese Medical Sciences
Corresponding Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Zhang C.,Jia X.,Bao J.,et al. Polyphyllin VII induces apoptosis in HepG2 cells through ROS-mediated mitochondrial dysfunction and MAPK pathways[J]. BMC complementary and alternative medicine,2016,16:58.
APA Zhang C..,Jia X..,Bao J..,Chen S..,Wang K..,...&He C..(2016).Polyphyllin VII induces apoptosis in HepG2 cells through ROS-mediated mitochondrial dysfunction and MAPK pathways.BMC complementary and alternative medicine,16,58.
MLA Zhang C.,et al."Polyphyllin VII induces apoptosis in HepG2 cells through ROS-mediated mitochondrial dysfunction and MAPK pathways".BMC complementary and alternative medicine 16(2016):58.
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