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Conference Paper: Inhibitory Effect of Embelin On Colon Carcinogenesis Is Peroxisome Proliferator-Activated Receptor γ (PPARγ)-Dependent

TitleInhibitory Effect of Embelin On Colon Carcinogenesis Is Peroxisome Proliferator-Activated Receptor γ (PPARγ)-Dependent
Authors
Issue Date2009
PublisherW.B. Saunders Co.
Citation
The 2009 Digestive Disease Week (DDW 2009), Chicago, IL., 30 May-4 June 2009. In Gastroenterology, 2009, v. 136 n. 5 suppl. 1, p, A-617–A-618, abstract no. T2001 How to Cite?
AbstractBACKGROUND AND OBJECTIVES We have recently observed that down-regulation of X-linked inhibitor of apoptosis protein (XIAP) sensitizes colon cancer cells to the anticancer effect of PPARγ ligands in mice. In this study, we aimed to evaluate the effect of Embelin (EB), a reported antagonist of XIAP, on colon cancer cells In Vitro and In Vivo, with a particular focus on whether PPARγ is required for EB to exert its effect. MATERIALS AND METHODS Colon cancer cell line HCT116 cells were used for In Vitro study. A dominant negative PPARγ (dnPPARγ) was used to antagonize endogenous PPARγ in HCT116 cells. Cell proliferation and apoptosis were measured by Annexin V/PI staining and Cell Death ELISA. Effect of EB on NF-κB activity was determined by luciferase assay. For In Vivo studies, colon specific carcinogen 1, 2-Dimethylhydrazine dihydrochloride (DMH) was subcutaneously injected to induce colon cancer in PPARγ+/+ and PPARγ +/- mice. Mice were fed EB daily for 10 days before DMH injection, and continued for 30 more weeks. MATERIALS AND METHODS Colon cancer cell line HCT116 cells were used for In Vitro study. A dominant negative PPARγ (dnPPARγ) was used to antagonize endogenous PPARγ in HCT116 cells. Cell proliferation was measured by [3H]-thymidine incorporation assay, and apoptosis was determined by Annexin V/PI staining and Cell Death ELISA. Effect of EB on NF-κB activity was determined by a non-radioactive chemiluminescent activity assay and luciferase assay. For In Vivo studies, colon specific carcinogen 1,2-Dimethylhydrazine dihydrochloride (DMH) was subcutaneously injected to induce colon cancer in PPARγ+/+ and PPARγ +/- mice. Mice were fed EB daily for 10 days before DMH injection, and continued for 30 more weeks. RESULTS EB inhibited the proliferation and induced apoptosis in HCT116 cells with marked up-regulation of PPARγ. DnPPARγ markedly abrogated the effects of EB In Vitro. PPARγ+/- mice were more susceptible to DMH-induced colon carcinogenesis than PPARγ+/+ mice. EB significantly reduced the incidence of colon cancer in PPARγ+/+ but not in PPARγ+/- mice. EB inhibited NF-κB activity in PPARγ+/+ but marginally so in PPARγ+/- mice. In addition, EB significantly inhibited the expression of Survivin and cMyc, and this inhibition was PPARγ -dependent. CONCLUSION Reduced expression of PPARγ significantly sensitizes DMH-induced colon carcinogenesis. EB exerts an inhibitory effect on colon carcinogenesis but this effect was dependent on the presence of functional PPARγ.
DescriptionThis journal suppl. entitled: 2009 DDW Abstract Supplement
Persistent Identifierhttp://hdl.handle.net/10722/62396
ISSN
2014 Impact Factor: 16.716
2014 SCImago Journal Rankings: 5.616

 

DC FieldValueLanguage
dc.contributor.authorDai, Yen_HK
dc.contributor.authorQiao, Len_HK
dc.contributor.authorChan, KWen_HK
dc.contributor.authorMa, Jen_HK
dc.contributor.authorZou, Ben_HK
dc.contributor.authorGu, Qen_HK
dc.contributor.authorWang, Jen_HK
dc.contributor.authorPang, RWCen_HK
dc.contributor.authorLan, HYen_HK
dc.contributor.authorWong, BCYen_HK
dc.date.accessioned2010-07-13T04:00:20Z-
dc.date.available2010-07-13T04:00:20Z-
dc.date.issued2009en_HK
dc.identifier.citationThe 2009 Digestive Disease Week (DDW 2009), Chicago, IL., 30 May-4 June 2009. In Gastroenterology, 2009, v. 136 n. 5 suppl. 1, p, A-617–A-618, abstract no. T2001-
dc.identifier.issn0016-5085-
dc.identifier.urihttp://hdl.handle.net/10722/62396-
dc.descriptionThis journal suppl. entitled: 2009 DDW Abstract Supplement-
dc.description.abstractBACKGROUND AND OBJECTIVES We have recently observed that down-regulation of X-linked inhibitor of apoptosis protein (XIAP) sensitizes colon cancer cells to the anticancer effect of PPARγ ligands in mice. In this study, we aimed to evaluate the effect of Embelin (EB), a reported antagonist of XIAP, on colon cancer cells In Vitro and In Vivo, with a particular focus on whether PPARγ is required for EB to exert its effect. MATERIALS AND METHODS Colon cancer cell line HCT116 cells were used for In Vitro study. A dominant negative PPARγ (dnPPARγ) was used to antagonize endogenous PPARγ in HCT116 cells. Cell proliferation and apoptosis were measured by Annexin V/PI staining and Cell Death ELISA. Effect of EB on NF-κB activity was determined by luciferase assay. For In Vivo studies, colon specific carcinogen 1, 2-Dimethylhydrazine dihydrochloride (DMH) was subcutaneously injected to induce colon cancer in PPARγ+/+ and PPARγ +/- mice. Mice were fed EB daily for 10 days before DMH injection, and continued for 30 more weeks. MATERIALS AND METHODS Colon cancer cell line HCT116 cells were used for In Vitro study. A dominant negative PPARγ (dnPPARγ) was used to antagonize endogenous PPARγ in HCT116 cells. Cell proliferation was measured by [3H]-thymidine incorporation assay, and apoptosis was determined by Annexin V/PI staining and Cell Death ELISA. Effect of EB on NF-κB activity was determined by a non-radioactive chemiluminescent activity assay and luciferase assay. For In Vivo studies, colon specific carcinogen 1,2-Dimethylhydrazine dihydrochloride (DMH) was subcutaneously injected to induce colon cancer in PPARγ+/+ and PPARγ +/- mice. Mice were fed EB daily for 10 days before DMH injection, and continued for 30 more weeks. RESULTS EB inhibited the proliferation and induced apoptosis in HCT116 cells with marked up-regulation of PPARγ. DnPPARγ markedly abrogated the effects of EB In Vitro. PPARγ+/- mice were more susceptible to DMH-induced colon carcinogenesis than PPARγ+/+ mice. EB significantly reduced the incidence of colon cancer in PPARγ+/+ but not in PPARγ+/- mice. EB inhibited NF-κB activity in PPARγ+/+ but marginally so in PPARγ+/- mice. In addition, EB significantly inhibited the expression of Survivin and cMyc, and this inhibition was PPARγ -dependent. CONCLUSION Reduced expression of PPARγ significantly sensitizes DMH-induced colon carcinogenesis. EB exerts an inhibitory effect on colon carcinogenesis but this effect was dependent on the presence of functional PPARγ.-
dc.languageengen_HK
dc.publisherW.B. Saunders Co.-
dc.relation.ispartofGastroenterology-
dc.titleInhibitory Effect of Embelin On Colon Carcinogenesis Is Peroxisome Proliferator-Activated Receptor γ (PPARγ)-Dependenten_HK
dc.typeConference_Paperen_HK
dc.identifier.emailDai, Y: daiyun1@medmail.com.cnen_HK
dc.identifier.emailQiao, L: lq8688@hotmail.comen_HK
dc.identifier.emailChan, KW: hrmtckw@hku.hken_HK
dc.identifier.emailMa, J: majuan00@hkucc.hku.hken_HK
dc.identifier.emailZou, B: zoubing@hkucc.hku.hken_HK
dc.identifier.emailGu, Q: qingappl@hotmail.comen_HK
dc.identifier.emailWang, J: jidewang@gmail.comen_HK
dc.identifier.emailPang, RWC: robertap@hku.hken_HK
dc.identifier.emailLan, HY: hylan@hku.hken_HK
dc.identifier.emailWong, BCY: bcywong@hku.hken_HK
dc.identifier.authorityQiao, L=rp00513en_HK
dc.identifier.authorityChan, KW=rp00330en_HK
dc.identifier.authorityWang, J=rp00491en_HK
dc.identifier.authorityWong, BCY=rp00429en_HK
dc.identifier.doi10.1016/S0016-5085(09)62847-X-
dc.identifier.hkuros155762en_HK
dc.identifier.volume136-
dc.identifier.issue5 suppl. 1-
dc.identifier.spageA-617, abstract no. T2001-
dc.identifier.epageA-618-

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