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Article: Peroxisome proliferator-activated receptor-γ contributes to the inhibitory effects of embelin on colon carcinogenesis

TitlePeroxisome proliferator-activated receptor-γ contributes to the inhibitory effects of embelin on colon carcinogenesis
Authors
Issue Date2009
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/
Citation
Cancer Research, 2009, v. 69 n. 11, p. 4776-4783 How to Cite?
AbstractDown-regulation of XIAP (X-linked inhibitor of apoptosis protein) sensitizes colon cancer cells to the anticancer effect of peroxisome proliferator-activated receptor-γ (PPARγ) ligands in mice. The aims of this study were to evaluate the effect of embelin (2,5-dihydroxy-3-undecyl-1, 4-benzoquinone), an antagonist of XIAP, on colon cancer, with a particular focus on whether PPARγ is required for embelin to exert its effect. A dominant-negative PPARγ was used to antagonize endogenous PPARγ in HCT116 cells. Cells were treated with or without embelin. Cell proliferation, apoptosis, and nuclear factor-κB (NF-κB) activity were measured. For in vivo studies, 1,2-dimethylhydrazine dihydrochloride (DMH) was s.c. injected to induce colon cancer in PPARγ +/+ and PPARγ +/- mice. Mice were fed embelin daily for 10 days before DMH injection, and continued for 30 more weeks. Embelin inhibited proliferation and induced apoptosis in HCT116 cells with marked up-regulation of PPARγ. In addition, embelin significantly inhibited the expressions of survivin, cyclin D1, and c-Myc. These effects were partially dependent on PPARγ. PPARγ +/- mice were more susceptible to DMH-induced colon carcinogenesis than PPARγ +/+ mice, and embelin significantly reduced the incidence of colon cancer in PPARγ +/+ mice but not in PPARγ +/- mice. Embelin inhibited NF-κB activity in PPARγ +/+ mice but marginally so in PPARγ +/- mice. Thus, reduced expression of PPARγ significantly sensitizes colonic tissues to the carcinogenic effect of DMH. Embelin inhibits chemical carcinogen-induced colon carcinogenesis, but this effect is partially dependent on the presence of functional PPARγ, indicating that PPARγ is a necessary signaling pathway involved in the antitumor activity of normal organisms. ©2009 American Association for Cancer Research.
Persistent Identifierhttp://hdl.handle.net/10722/163248
ISSN
2015 Impact Factor: 8.556
2015 SCImago Journal Rankings: 5.372
ISI Accession Number ID
Funding AgencyGrant Number
Simon K.Y. Lee endowed professorship Research Fund
Gordon Chiu Stomach Cancer Research Fund
Outstanding Researcher Award Fund of the University of Hong Kong, Hong Kong
University of Hong Kong Seed Funding10206827.49710.20600.302.01
Funding Information:

Grant support: Simon K.Y. Lee endowed professorship Research Fund, Gordon Chiu Stomach Cancer Research Fund, and Outstanding Researcher Award Fund of the University of Hong Kong, Hong Kong. Drs. Liang Qiao and Yun Dai were partially supported by the University of Hong Kong Seed Funding programs (grant code: 10206827.49710.20600.302.01).

References

 

DC FieldValueLanguage
dc.contributor.authorDai, Yen_HK
dc.contributor.authorQiao, Len_HK
dc.contributor.authorKwok, WCen_HK
dc.contributor.authorYang, Men_HK
dc.contributor.authorYe, Jen_HK
dc.contributor.authorMa, Jen_HK
dc.contributor.authorZou, Ben_HK
dc.contributor.authorGu, Qen_HK
dc.contributor.authorWang, Jen_HK
dc.contributor.authorPang, Ren_HK
dc.contributor.authorLan, HYen_HK
dc.contributor.authorWong, BCYen_HK
dc.date.accessioned2012-09-05T05:29:07Z-
dc.date.available2012-09-05T05:29:07Z-
dc.date.issued2009en_HK
dc.identifier.citationCancer Research, 2009, v. 69 n. 11, p. 4776-4783en_HK
dc.identifier.issn0008-5472en_HK
dc.identifier.urihttp://hdl.handle.net/10722/163248-
dc.description.abstractDown-regulation of XIAP (X-linked inhibitor of apoptosis protein) sensitizes colon cancer cells to the anticancer effect of peroxisome proliferator-activated receptor-γ (PPARγ) ligands in mice. The aims of this study were to evaluate the effect of embelin (2,5-dihydroxy-3-undecyl-1, 4-benzoquinone), an antagonist of XIAP, on colon cancer, with a particular focus on whether PPARγ is required for embelin to exert its effect. A dominant-negative PPARγ was used to antagonize endogenous PPARγ in HCT116 cells. Cells were treated with or without embelin. Cell proliferation, apoptosis, and nuclear factor-κB (NF-κB) activity were measured. For in vivo studies, 1,2-dimethylhydrazine dihydrochloride (DMH) was s.c. injected to induce colon cancer in PPARγ +/+ and PPARγ +/- mice. Mice were fed embelin daily for 10 days before DMH injection, and continued for 30 more weeks. Embelin inhibited proliferation and induced apoptosis in HCT116 cells with marked up-regulation of PPARγ. In addition, embelin significantly inhibited the expressions of survivin, cyclin D1, and c-Myc. These effects were partially dependent on PPARγ. PPARγ +/- mice were more susceptible to DMH-induced colon carcinogenesis than PPARγ +/+ mice, and embelin significantly reduced the incidence of colon cancer in PPARγ +/+ mice but not in PPARγ +/- mice. Embelin inhibited NF-κB activity in PPARγ +/+ mice but marginally so in PPARγ +/- mice. Thus, reduced expression of PPARγ significantly sensitizes colonic tissues to the carcinogenic effect of DMH. Embelin inhibits chemical carcinogen-induced colon carcinogenesis, but this effect is partially dependent on the presence of functional PPARγ, indicating that PPARγ is a necessary signaling pathway involved in the antitumor activity of normal organisms. ©2009 American Association for Cancer Research.en_HK
dc.languageengen_US
dc.publisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/en_HK
dc.relation.ispartofCancer Researchen_HK
dc.subject.meshAdenocarcinoma - Genetics - Metabolism - Pathology - Prevention & Controlen_US
dc.subject.meshAnimalsen_US
dc.subject.meshAntineoplastic Agents - Pharmacology - Therapeutic Useen_US
dc.subject.meshApoptosis - Drug Effectsen_US
dc.subject.meshBenzoquinones - Pharmacology - Therapeutic Useen_US
dc.subject.meshCell Proliferation - Drug Effectsen_US
dc.subject.meshColonic Neoplasms - Genetics - Metabolism - Pathology - Prevention & Controlen_US
dc.subject.meshDrug Evaluation, Preclinicalen_US
dc.subject.meshFemaleen_US
dc.subject.meshGene Expression Regulation, Neoplastic - Drug Effectsen_US
dc.subject.meshHct116 Cellsen_US
dc.subject.meshHumansen_US
dc.subject.meshMaleen_US
dc.subject.meshMiceen_US
dc.subject.meshMice, Inbred C57blen_US
dc.subject.meshMice, Transgenicen_US
dc.subject.meshNf-Kappa B - Metabolismen_US
dc.subject.meshPpar Gamma - Antagonists & Inhibitors - Physiologyen_US
dc.subject.meshSignal Transduction - Drug Effectsen_US
dc.titlePeroxisome proliferator-activated receptor-γ contributes to the inhibitory effects of embelin on colon carcinogenesisen_HK
dc.typeArticleen_HK
dc.identifier.emailQiao, L: lq8688@hotmail.comen_HK
dc.identifier.emailWang, J: jidewang@gmail.comen_HK
dc.identifier.emailPang, R: robertap@hku.hken_HK
dc.identifier.emailWong, BCY: bcywong@hku.hken_HK
dc.identifier.authorityQiao, L=rp00513en_HK
dc.identifier.authorityWang, J=rp00491en_HK
dc.identifier.authorityPang, R=rp00274en_HK
dc.identifier.authorityWong, BCY=rp00429en_HK
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1158/0008-5472.CAN-08-4754en_HK
dc.identifier.pmid19458067-
dc.identifier.scopuseid_2-s2.0-66349089835en_HK
dc.identifier.hkuros155716-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-66349089835&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume69en_HK
dc.identifier.issue11en_HK
dc.identifier.spage4776en_HK
dc.identifier.epage4783en_HK
dc.identifier.eissn1538-7445-
dc.identifier.isiWOS:000266755000030-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridDai, Y=7401512993en_HK
dc.identifier.scopusauthoridQiao, L=7202151719en_HK
dc.identifier.scopusauthoridKwok, WC=24171150800en_HK
dc.identifier.scopusauthoridYang, M=7404927250en_HK
dc.identifier.scopusauthoridYe, J=23669624100en_HK
dc.identifier.scopusauthoridMa, J=35275386200en_HK
dc.identifier.scopusauthoridZou, B=35228257300en_HK
dc.identifier.scopusauthoridGu, Q=24469982400en_HK
dc.identifier.scopusauthoridWang, J=35309087500en_HK
dc.identifier.scopusauthoridPang, R=7004376659en_HK
dc.identifier.scopusauthoridLan, HY=7102710832en_HK
dc.identifier.scopusauthoridWong, BCY=7402023340en_HK

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