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20(S)-Protopanaxadiol, a metabolite of ginsenosides, induced cell apoptosis through endoplasmic reticulum stress in human hepatocarcinoma HepG2 cells
Zhu G.-Y.; Li Y.-W.; Tse A.K.-W.; Hau D.K.-P.; Leung C.-H.; Yu Z.-L.; Fong W.-F.
2011-10-01
Source PublicationEuropean Journal of Pharmacology
ISSN00142999 18790712
Volume668Issue:1-2Pages:88-98
Abstract20(S)-Protopanaxadiol (PPD), a metabolite of ginsenosides, has been demonstrated to possess cytotoxic effects on several cancer cell lines. The molecular mechanism is, however, not well understood. In this study, we have shown that PPD inhibits cell growth and induces apoptosis in human hepatocarcinoma HepG2 cells. PPD-treated cells showed a massive cytoplasmic vacuolization and a dramatic change of endoplasmic reticulum (ER) morphology. The induction of ER stress is associated with the upregulation of ER stress-associated genes and proteins. PPD activates the unfolded protein response (UPR) through the phosphorylation of PERK and eIF2α, the splicing of XBP1 mRNA, and the cleavage of AFT6. PPD also induces the intrinsic and extrinsic apoptotic pathways. It activates DR5, caspase-8, -9, -3, and promotes the cleavage of PARP while it downregulates Bcl-2, Bcl-x and mitochondrial membrane potential. Knockdown of one of the three UPR limbs by specific siRNAs did not affect PPD-induced apoptosis, which was however, significantly suppressed by the downregulation of CHOP. Western blot analysis showed that PPD-stimulated downregulation of Bcl-2 protein, increase of DR5 protein, activation of caspase-8 and cleavage of PARP were significantly inhibited in CHOP siRNA-transfected cells. Taken together, we have identified ER as a molecular target of PPD and our data support the hypothesis that PPD induces HepG2 cell apoptosis through the ER stress pathway. © 2011 Elsevier B.V.
Keyword20(S)-Protopanaxadiol Apoptosis CHOP Endoplasmic reticulum stress Ginseng Human hepatocarcinoma
DOI10.1016/j.ejphar.2011.06.008
URLView the original
Language英語
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Cited Times [WOS]:39   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
AffiliationHong Kong Baptist University
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Zhu G.-Y.,Li Y.-W.,Tse A.K.-W.,et al. 20(S)-Protopanaxadiol, a metabolite of ginsenosides, induced cell apoptosis through endoplasmic reticulum stress in human hepatocarcinoma HepG2 cells[J]. European Journal of Pharmacology,2011,668(1-2):88-98.
APA Zhu G.-Y..,Li Y.-W..,Tse A.K.-W..,Hau D.K.-P..,Leung C.-H..,...&Fong W.-F..(2011).20(S)-Protopanaxadiol, a metabolite of ginsenosides, induced cell apoptosis through endoplasmic reticulum stress in human hepatocarcinoma HepG2 cells.European Journal of Pharmacology,668(1-2),88-98.
MLA Zhu G.-Y.,et al."20(S)-Protopanaxadiol, a metabolite of ginsenosides, induced cell apoptosis through endoplasmic reticulum stress in human hepatocarcinoma HepG2 cells".European Journal of Pharmacology 668.1-2(2011):88-98.
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