A chemoprotective fish oil/pectin diet enhances apoptosis via Bcl-2 promoter methylation in rat azoxymethane-induced carcinomas

Cho, Y; Turner, ND; Davidson, LA; Chapkin, RS; Carroll, RJ; Lupton, JR

A chemoprotective fish oil/pectin diet enhances apoptosis via Bcl-2 promoter methylation in rat azoxymethane-induced carcinomas

Cho, Y Turner, ND Davidson, LA Chapkin, RS Carroll, RJ Lupton, JR

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Publication Type:: Journal Article
Citation:: Experimental Biology and Medicine, 2012, 237 (12), pp. 1387 - 1393
Issue Date:: 2012-12-01

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Field	Value	Language
dc.contributor.author	Cho, Y	en_US
dc.contributor.author	Turner, ND	en_US
dc.contributor.author	Davidson, LA	en_US
dc.contributor.author	Chapkin, RS	en_US
dc.contributor.author	Carroll, RJ	en_US
dc.contributor.author	Lupton, JR	en_US
dc.date.issued	2012-12-01	en_US
dc.identifier.citation	Experimental Biology and Medicine, 2012, 237 (12), pp. 1387 - 1393	en_US
dc.identifier.issn	1535-3702	en_US
dc.identifier.uri	http://hdl.handle.net/10453/114918
dc.description.abstract	We have demonstrated that diets containing fish oil and pectin (FO/P) reduce colon tumor incidence relative to control (corn oil and cellulose [CO/C]) in part by inducing apoptosis of DNA-damaged colon cells. Relative to FO/P, CO/C promotes colonocyte expression of the antiapoptotic modulator, Bcl-2, and Bcl-2 promoter methylation is altered in colon cancer. To determine if FO/P, compared with CO/C, limits Bcl-2 expression by enhancing promoter methylation in colon tumors, we examined Bcl-2 promoter methylation, mRNA levels, colonocyte apoptosis and colon tumor incidence in azoxymethane (AOM)-injected rats. Rats were provided diets containing FO/P or CO/C, and were terminated 16 and 34 weeks after AOM injection. DNA isolated from paraformaldehyde-fixed colon tumors and uninvolved tissue was bisulfite modified and amplified by quantitative reverese transcriptase-polymerase chain reaction to assess DNA methylation in Bcl-2 cytosine-guanosine islands. FO/P increased Bcl-2 promoter methylation (P = 0.009) in tumor tissues and colonocyte apoptosis (P = 0.020) relative to CO/C. An inverse correlation between Bcl-2 DNA methylation and Bcl-2 mRNA levels was observed in the tumors. We conclude that dietary FO/P promotes apoptosis in part by enhancing Bcl-2 promoter methylation. These Bcl-2 promoter methylation responses, measured in vivo, contribute to our understanding of the mechanisms involved in chemoprevention of colon cancer by diets containing FO/P. © 2008 Society for Experimental Biology and Medicine.	en_US
dc.relation.ispartof	Experimental Biology and Medicine	en_US
dc.relation.isbasedon	10.1258/ebm.2012.012244	en_US
dc.subject.classification	Biochemistry & Molecular Biology	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Rats	en_US
dc.subject.mesh	Rats, Sprague-Dawley	en_US
dc.subject.mesh	Colonic Neoplasms	en_US
dc.subject.mesh	Neoplasms, Experimental	en_US
dc.subject.mesh	Azo Compounds	en_US
dc.subject.mesh	Pectins	en_US
dc.subject.mesh	Fish Oils	en_US
dc.subject.mesh	Proto-Oncogene Proteins c-bcl-2	en_US
dc.subject.mesh	DNA, Neoplasm	en_US
dc.subject.mesh	RNA, Messenger	en_US
dc.subject.mesh	RNA, Neoplasm	en_US
dc.subject.mesh	Diet	en_US
dc.subject.mesh	Apoptosis	en_US
dc.subject.mesh	DNA Methylation	en_US
dc.subject.mesh	Gene Expression Regulation, Neoplastic	en_US
dc.subject.mesh	Male	en_US
dc.subject.mesh	Promoter Regions, Genetic	en_US
dc.title	A chemoprotective fish oil/pectin diet enhances apoptosis via Bcl-2 promoter methylation in rat azoxymethane-induced carcinomas	en_US
dc.type	Journal Article
utslib.citation.volume	12	en_US
utslib.citation.volume	237	en_US
utslib.for	11 Medical and Health Sciences	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Mathematical and Physical Sciences
utslib.copyright.status	closed_access
pubs.issue	12	en_US
pubs.publication-status	Published	en_US
pubs.volume	237	en_US

Abstract:

We have demonstrated that diets containing fish oil and pectin (FO/P) reduce colon tumor incidence relative to control (corn oil and cellulose [CO/C]) in part by inducing apoptosis of DNA-damaged colon cells. Relative to FO/P, CO/C promotes colonocyte expression of the antiapoptotic modulator, Bcl-2, and Bcl-2 promoter methylation is altered in colon cancer. To determine if FO/P, compared with CO/C, limits Bcl-2 expression by enhancing promoter methylation in colon tumors, we examined Bcl-2 promoter methylation, mRNA levels, colonocyte apoptosis and colon tumor incidence in azoxymethane (AOM)-injected rats. Rats were provided diets containing FO/P or CO/C, and were terminated 16 and 34 weeks after AOM injection. DNA isolated from paraformaldehyde-fixed colon tumors and uninvolved tissue was bisulfite modified and amplified by quantitative reverese transcriptase-polymerase chain reaction to assess DNA methylation in Bcl-2 cytosine-guanosine islands. FO/P increased Bcl-2 promoter methylation (P = 0.009) in tumor tissues and colonocyte apoptosis (P = 0.020) relative to CO/C. An inverse correlation between Bcl-2 DNA methylation and Bcl-2 mRNA levels was observed in the tumors. We conclude that dietary FO/P promotes apoptosis in part by enhancing Bcl-2 promoter methylation. These Bcl-2 promoter methylation responses, measured in vivo, contribute to our understanding of the mechanisms involved in chemoprevention of colon cancer by diets containing FO/P. © 2008 Society for Experimental Biology and Medicine.

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http://hdl.handle.net/10453/114918