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Chemoprevention of hepatocarcinogenesis on rats during the promotion phase treated with tributyrin, a food bioactive compound: aspects of genes pathways that code for p53 and p33ING1b

Grant number: 09/53407-5
Support type:Regular Research Grants
Duration: May 01, 2010 - April 30, 2012
Field of knowledge:Health Sciences - Nutrition - Nutrition Biochemistry
Principal Investigator:Fernando Salvador Moreno
Grantee:Fernando Salvador Moreno
Home Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Bioactive compounds present in foods (CBAs) are able to modulate distinct biological processes related to cancer chemoprevention, however their mechanisms of action are few understood. Epigenetic events, including DNA methylation and histones modifications, are potentially reversible, being considered targets for cancer chemoprevention. Recently, we found that tributyrin (TB), CBA present in the milk fat and honey, presented hepatocarcinogenesis chemopreventive activity in rats and this could be related to histones acetylation induction and to p53 cytoplasmic accumulation. Modulation pathways and subcelular localization of p53 may be involved with pre-neoplasic lesions (PNLs). The tumor suppressor protein p33ING1b that inhibits p53 degradation was found silenced by epigenetic mechanisms in many types of cancers, including hepatocarcinomas. In this context, we aim to investigate the TB chemopreventive effects in rats treated in promotion phase of hepatocarcinogenesis, as - well as, elucidate mechanisms by which exerts its protector effect. Therefore, the following parameters will be evalueted in persistents and remodeling PNLs, as well as, in the surrounding liver tissue considered normal: expression and localization of p53, p33ING1b and of proteins involved with the nucleo-cytoplasmatic shuttling of p53 (importin a, Mdm2, CRM1, PARC, ARC and RanBP1), expression of acetylated H3K9, methylated H3K4 and p21, as well as, evaluate the methylation and acetylation status of the promoter region of the gene that encode for p33ING1b. (AU)