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Article: 20(S)-Protopanaxadiol, a metabolite of ginsenosides, induced cell apoptosis through endoplasmic reticulum stress in human hepatocarcinoma HepG2 cells

Title20(S)-Protopanaxadiol, a metabolite of ginsenosides, induced cell apoptosis through endoplasmic reticulum stress in human hepatocarcinoma HepG2 cells
Authors
Issue Date2011
PublisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/ejphar
Citation
European Journal Of Pharmacology, 2011, v. 668 n. 1-2, p. 88-98 How to Cite?
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 L 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.
Persistent Identifierhttp://hdl.handle.net/10722/168558
ISSN
2015 Impact Factor: 2.73
2015 SCImago Journal Rankings: 1.115
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorZhu, GYen_US
dc.contributor.authorLi, YWen_US
dc.contributor.authorTse, AKWen_US
dc.contributor.authorHau, DKPen_US
dc.contributor.authorLeung, CHen_US
dc.contributor.authorYu, ZLen_US
dc.contributor.authorFong, WFen_US
dc.date.accessioned2012-10-08T03:20:38Z-
dc.date.available2012-10-08T03:20:38Z-
dc.date.issued2011en_US
dc.identifier.citationEuropean Journal Of Pharmacology, 2011, v. 668 n. 1-2, p. 88-98en_US
dc.identifier.issn0014-2999en_US
dc.identifier.urihttp://hdl.handle.net/10722/168558-
dc.description.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 L 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.en_US
dc.languageengen_US
dc.publisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/ejpharen_US
dc.relation.ispartofEuropean Journal of Pharmacologyen_US
dc.subject.meshApoptosis - Drug Effectsen_US
dc.subject.meshEndoplasmic Reticulum Stress - Drug Effectsen_US
dc.subject.meshExtracellular Signal-Regulated Map Kinases - Metabolismen_US
dc.subject.meshGinsenosides - Metabolismen_US
dc.subject.meshHep G2 Cellsen_US
dc.subject.meshHumansen_US
dc.subject.meshLiver Neoplasms - Pathologyen_US
dc.subject.meshMap Kinase Signaling System - Drug Effectsen_US
dc.subject.meshMitochondria - Drug Effects - Metabolismen_US
dc.subject.meshReceptors, Tnf-Related Apoptosis-Inducing Ligand - Metabolismen_US
dc.subject.meshSapogenins - Metabolism - Pharmacologyen_US
dc.subject.meshTranscription Factor Chop - Metabolismen_US
dc.subject.meshUnfolded Protein Response - Drug Effectsen_US
dc.subject.meshUp-Regulation - Drug Effectsen_US
dc.subject.meshVacuoles - Drug Effects - Metabolismen_US
dc.subject.meshP38 Mitogen-Activated Protein Kinases - Metabolismen_US
dc.title20(S)-Protopanaxadiol, a metabolite of ginsenosides, induced cell apoptosis through endoplasmic reticulum stress in human hepatocarcinoma HepG2 cellsen_US
dc.typeArticleen_US
dc.identifier.emailLeung, CH:duncanl@hkucc.hku.hken_US
dc.identifier.authorityLeung, CH=rp00730en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1016/j.ejphar.2011.06.008en_US
dc.identifier.pmid21703260-
dc.identifier.scopuseid_2-s2.0-80052064898en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-80052064898&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume668en_US
dc.identifier.issue1-2en_US
dc.identifier.spage88en_US
dc.identifier.epage98en_US
dc.identifier.isiWOS:000303048100011-
dc.publisher.placeNetherlandsen_US
dc.identifier.scopusauthoridZhu, GY=7402633140en_US
dc.identifier.scopusauthoridLi, YW=36337641300en_US
dc.identifier.scopusauthoridTse, AKW=7005306729en_US
dc.identifier.scopusauthoridHau, DKP=12775935300en_US
dc.identifier.scopusauthoridLeung, CH=7402612570en_US
dc.identifier.scopusauthoridYu, ZL=15048950700en_US
dc.identifier.scopusauthoridFong, WF=7102816013en_US
dc.identifier.citeulike9494090-

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