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- Publisher Website: 10.1158/0008-5472.CAN-08-4754
- Scopus: eid_2-s2.0-66349089835
- PMID: 19458067
- WOS: WOS:000266755000030
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Article: Peroxisome proliferator-activated receptor-γ contributes to the inhibitory effects of embelin on colon carcinogenesis
Title | Peroxisome proliferator-activated receptor-γ contributes to the inhibitory effects of embelin on colon carcinogenesis | ||||||||||
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Authors | |||||||||||
Issue Date | 2009 | ||||||||||
Publisher | American 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? | ||||||||||
Abstract | Down-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 Identifier | http://hdl.handle.net/10722/163248 | ||||||||||
ISSN | 2023 Impact Factor: 12.5 2023 SCImago Journal Rankings: 3.468 | ||||||||||
ISI Accession Number ID |
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 Field | Value | Language |
---|---|---|
dc.contributor.author | Dai, Y | en_HK |
dc.contributor.author | Qiao, L | en_HK |
dc.contributor.author | Kwok, WC | en_HK |
dc.contributor.author | Yang, M | en_HK |
dc.contributor.author | Ye, J | en_HK |
dc.contributor.author | Ma, J | en_HK |
dc.contributor.author | Zou, B | en_HK |
dc.contributor.author | Gu, Q | en_HK |
dc.contributor.author | Wang, J | en_HK |
dc.contributor.author | Pang, R | en_HK |
dc.contributor.author | Lan, HY | en_HK |
dc.contributor.author | Wong, BCY | en_HK |
dc.date.accessioned | 2012-09-05T05:29:07Z | - |
dc.date.available | 2012-09-05T05:29:07Z | - |
dc.date.issued | 2009 | en_HK |
dc.identifier.citation | Cancer Research, 2009, v. 69 n. 11, p. 4776-4783 | en_HK |
dc.identifier.issn | 0008-5472 | en_HK |
dc.identifier.uri | http://hdl.handle.net/10722/163248 | - |
dc.description.abstract | Down-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.language | eng | en_US |
dc.publisher | American Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/ | en_HK |
dc.relation.ispartof | Cancer Research | en_HK |
dc.subject.mesh | Adenocarcinoma - Genetics - Metabolism - Pathology - Prevention & Control | en_US |
dc.subject.mesh | Animals | en_US |
dc.subject.mesh | Antineoplastic Agents - Pharmacology - Therapeutic Use | en_US |
dc.subject.mesh | Apoptosis - Drug Effects | en_US |
dc.subject.mesh | Benzoquinones - Pharmacology - Therapeutic Use | en_US |
dc.subject.mesh | Cell Proliferation - Drug Effects | en_US |
dc.subject.mesh | Colonic Neoplasms - Genetics - Metabolism - Pathology - Prevention & Control | en_US |
dc.subject.mesh | Drug Evaluation, Preclinical | en_US |
dc.subject.mesh | Female | en_US |
dc.subject.mesh | Gene Expression Regulation, Neoplastic - Drug Effects | en_US |
dc.subject.mesh | Hct116 Cells | en_US |
dc.subject.mesh | Humans | en_US |
dc.subject.mesh | Male | en_US |
dc.subject.mesh | Mice | en_US |
dc.subject.mesh | Mice, Inbred C57bl | en_US |
dc.subject.mesh | Mice, Transgenic | en_US |
dc.subject.mesh | Nf-Kappa B - Metabolism | en_US |
dc.subject.mesh | Ppar Gamma - Antagonists & Inhibitors - Physiology | en_US |
dc.subject.mesh | Signal Transduction - Drug Effects | en_US |
dc.title | Peroxisome proliferator-activated receptor-γ contributes to the inhibitory effects of embelin on colon carcinogenesis | en_HK |
dc.type | Article | en_HK |
dc.identifier.email | Qiao, L: lq8688@hotmail.com | en_HK |
dc.identifier.email | Wang, J: jidewang@gmail.com | en_HK |
dc.identifier.email | Pang, R: robertap@hku.hk | en_HK |
dc.identifier.email | Wong, BCY: bcywong@hku.hk | en_HK |
dc.identifier.authority | Qiao, L=rp00513 | en_HK |
dc.identifier.authority | Wang, J=rp00491 | en_HK |
dc.identifier.authority | Pang, R=rp00274 | en_HK |
dc.identifier.authority | Wong, BCY=rp00429 | en_HK |
dc.description.nature | link_to_subscribed_fulltext | en_US |
dc.identifier.doi | 10.1158/0008-5472.CAN-08-4754 | en_HK |
dc.identifier.pmid | 19458067 | - |
dc.identifier.scopus | eid_2-s2.0-66349089835 | en_HK |
dc.identifier.hkuros | 155716 | - |
dc.relation.references | http://www.scopus.com/mlt/select.url?eid=2-s2.0-66349089835&selection=ref&src=s&origin=recordpage | en_HK |
dc.identifier.volume | 69 | en_HK |
dc.identifier.issue | 11 | en_HK |
dc.identifier.spage | 4776 | en_HK |
dc.identifier.epage | 4783 | en_HK |
dc.identifier.eissn | 1538-7445 | - |
dc.identifier.isi | WOS:000266755000030 | - |
dc.publisher.place | United States | en_HK |
dc.identifier.scopusauthorid | Dai, Y=7401512993 | en_HK |
dc.identifier.scopusauthorid | Qiao, L=7202151719 | en_HK |
dc.identifier.scopusauthorid | Kwok, WC=24171150800 | en_HK |
dc.identifier.scopusauthorid | Yang, M=7404927250 | en_HK |
dc.identifier.scopusauthorid | Ye, J=23669624100 | en_HK |
dc.identifier.scopusauthorid | Ma, J=35275386200 | en_HK |
dc.identifier.scopusauthorid | Zou, B=35228257300 | en_HK |
dc.identifier.scopusauthorid | Gu, Q=24469982400 | en_HK |
dc.identifier.scopusauthorid | Wang, J=35309087500 | en_HK |
dc.identifier.scopusauthorid | Pang, R=7004376659 | en_HK |
dc.identifier.scopusauthorid | Lan, HY=7102710832 | en_HK |
dc.identifier.scopusauthorid | Wong, BCY=7402023340 | en_HK |
dc.identifier.issnl | 0008-5472 | - |