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Article: Functional p53 is required for triptolide-induced apoptosis and AP-1 and nuclear factor-κB activation in gastric cancer cells

TitleFunctional p53 is required for triptolide-induced apoptosis and AP-1 and nuclear factor-κB activation in gastric cancer cells
Authors
Issue Date2001
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/onc
Citation
Oncogene, 2001, v. 20 n. 55, p. 8009-8018 How to Cite?
AbstractTriptolide, a major component in the extract of Chinese herbal plant Tripterygium wilfordii Hook f (TWHf), has potential anti-neoplastic effect. In the present study we investigated the potential therapeutic effects and mechanisms of triptolide against human gastric cancer cells. Four gastric cancer cell lines with different p53 status, AGS and MKN-45 (wild type p53); MKN-28 and SGC-7901 (mutant p53) were observed as to cell growth inhibition and induction of apoptosis in response to triptolide treatment. We showed that triptolide inhibited cell growth, induced apoptosis and suppressed NK-κB and AP-1 transactivation in AGS cells with wild-type p53. Triptolide induced apoptosis by stimulating the expressions of p53, p21 waf1/cip1, bax protein, and increased the activity of caspases. In addition, it caused cell cycle arrest in the G 0/G 1 phase. To examine the role of p53 in these functions, we showed that suppression of p53 level with antisense oligonucleotide abrogated triptolide-induced apoptosis and over-expression of dominant negative p53 abolished the inhibitory effect on NF-κB activation. Furthermore, we demonstrated that triptolide had differential effects on gastric cancer cells with different p53 status. We showed that triptolide also inhibited cell growth and induced apoptosis in MKN-45 with wild-type p53, whereas it had no significant growth-inhibition and apoptosis induction effects on the MKN-28 and SGC-7901 cells with mutant p53. Our data suggest that triptolide exhibits anti-tumor and anti-inflammatory effects by inhibiting cell proliferation, inducing apoptosis and inhibiting NF-κB and AP-1 transcriptional activity. However, a functional p53 is required for these proapoptotic, anti-inflammatory and anti-tumor effects.
Persistent Identifierhttp://hdl.handle.net/10722/167721
ISSN
2015 Impact Factor: 7.932
2015 SCImago Journal Rankings: 4.047
References

 

DC FieldValueLanguage
dc.contributor.authorJiang, XHen_US
dc.contributor.authorWong, BCYen_US
dc.contributor.authorLin, MCMen_US
dc.contributor.authorZhu, GHen_US
dc.contributor.authorKung, HFen_US
dc.contributor.authorJiang, SHen_US
dc.contributor.authorYang, Den_US
dc.contributor.authorLam, SKen_US
dc.date.accessioned2012-10-08T03:10:26Z-
dc.date.available2012-10-08T03:10:26Z-
dc.date.issued2001en_US
dc.identifier.citationOncogene, 2001, v. 20 n. 55, p. 8009-8018en_US
dc.identifier.issn0950-9232en_US
dc.identifier.urihttp://hdl.handle.net/10722/167721-
dc.description.abstractTriptolide, a major component in the extract of Chinese herbal plant Tripterygium wilfordii Hook f (TWHf), has potential anti-neoplastic effect. In the present study we investigated the potential therapeutic effects and mechanisms of triptolide against human gastric cancer cells. Four gastric cancer cell lines with different p53 status, AGS and MKN-45 (wild type p53); MKN-28 and SGC-7901 (mutant p53) were observed as to cell growth inhibition and induction of apoptosis in response to triptolide treatment. We showed that triptolide inhibited cell growth, induced apoptosis and suppressed NK-κB and AP-1 transactivation in AGS cells with wild-type p53. Triptolide induced apoptosis by stimulating the expressions of p53, p21 waf1/cip1, bax protein, and increased the activity of caspases. In addition, it caused cell cycle arrest in the G 0/G 1 phase. To examine the role of p53 in these functions, we showed that suppression of p53 level with antisense oligonucleotide abrogated triptolide-induced apoptosis and over-expression of dominant negative p53 abolished the inhibitory effect on NF-κB activation. Furthermore, we demonstrated that triptolide had differential effects on gastric cancer cells with different p53 status. We showed that triptolide also inhibited cell growth and induced apoptosis in MKN-45 with wild-type p53, whereas it had no significant growth-inhibition and apoptosis induction effects on the MKN-28 and SGC-7901 cells with mutant p53. Our data suggest that triptolide exhibits anti-tumor and anti-inflammatory effects by inhibiting cell proliferation, inducing apoptosis and inhibiting NF-κB and AP-1 transcriptional activity. However, a functional p53 is required for these proapoptotic, anti-inflammatory and anti-tumor effects.en_US
dc.languageengen_US
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/oncen_US
dc.relation.ispartofOncogeneen_US
dc.subject.meshApoptosis - Drug Effectsen_US
dc.subject.meshBlotting, Westernen_US
dc.subject.meshCaspase 3en_US
dc.subject.meshCaspases - Metabolismen_US
dc.subject.meshCell Cycle - Drug Effectsen_US
dc.subject.meshCell Division - Drug Effectsen_US
dc.subject.meshCyclin-Dependent Kinase Inhibitor P21en_US
dc.subject.meshCyclins - Metabolismen_US
dc.subject.meshDna - Genetics - Metabolismen_US
dc.subject.meshDiterpenes - Pharmacologyen_US
dc.subject.meshDose-Response Relationship, Drugen_US
dc.subject.meshElectrophoretic Mobility Shift Assayen_US
dc.subject.meshEpoxy Compoundsen_US
dc.subject.meshFlow Cytometryen_US
dc.subject.meshGene Expression Regulation, Neoplastic - Drug Effectsen_US
dc.subject.meshHumansen_US
dc.subject.meshNf-Kappa B - Metabolismen_US
dc.subject.meshOligonucleotides, Antisense - Geneticsen_US
dc.subject.meshPhenanthrenesen_US
dc.subject.meshPoly(Adp-Ribose) Polymerases - Metabolismen_US
dc.subject.meshProtein Binding - Drug Effectsen_US
dc.subject.meshProto-Oncogene Proteins - Metabolismen_US
dc.subject.meshProto-Oncogene Proteins C-Bcl-2en_US
dc.subject.meshStomach Neoplasms - Metabolism - Pathologyen_US
dc.subject.meshTranscription Factor Ap-1 - Metabolismen_US
dc.subject.meshTranscriptional Activation - Drug Effectsen_US
dc.subject.meshTumor Cells, Cultureden_US
dc.subject.meshTumor Suppressor Protein P53 - Biosynthesis - Genetics - Metabolismen_US
dc.subject.meshBcl-2-Associated X Proteinen_US
dc.titleFunctional p53 is required for triptolide-induced apoptosis and AP-1 and nuclear factor-κB activation in gastric cancer cellsen_US
dc.typeArticleen_US
dc.identifier.emailWong, BCY:bcywong@hku.hken_US
dc.identifier.emailLin, MCM:mcllin@hkucc.hku.hken_US
dc.identifier.emailYang, D:yangdan@hku.hken_US
dc.identifier.authorityWong, BCY=rp00429en_US
dc.identifier.authorityLin, MCM=rp00746en_US
dc.identifier.authorityYang, D=rp00825en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1038/sj/onc/1204981en_US
dc.identifier.pmid11753684-
dc.identifier.scopuseid_2-s2.0-0035969633en_US
dc.identifier.hkuros68418-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0035969633&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume20en_US
dc.identifier.issue55en_US
dc.identifier.spage8009en_US
dc.identifier.epage8018en_US
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridJiang, XH=36089034900en_US
dc.identifier.scopusauthoridWong, BCY=7402023340en_US
dc.identifier.scopusauthoridLin, MCM=7404816359en_US
dc.identifier.scopusauthoridZhu, GH=7402633170en_US
dc.identifier.scopusauthoridKung, HF=7402514190en_US
dc.identifier.scopusauthoridJiang, SH=7404453122en_US
dc.identifier.scopusauthoridYang, D=7404800756en_US
dc.identifier.scopusauthoridLam, SK=7402279473en_US

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