title: Chemopreventive effects of the dietary histone deacetylase inhibitor tributyrin alone or in combination with vitamin A during the promotion phase of rat hepatocarcinogenesis.
abstract: The chemopreventive effects of tributyrin (TB) and vitamin A (VA), alone or in combination, were investigated during the promotion phase of rat hepatocarcinogenesis. Compared to diethylnitrosamine control rats, TB and TB+VA-treated rats, but not VA-treated rats, presented a lower incidence and mean number of hepatocyte nodules and a smaller size of persistent preneoplastic lesions (pPNLs). In addition, TB and TB+VA-treated rats exhibited a higher apoptotic body index in pPNL and remodeling PNL, whereas VA-treated rats presented only a higher apoptotic body index in remodeling PNL. None of the treatments inhibited cell proliferation in PNL. TB and TB+VA-treated rats, but not VA-treated rats, exhibited higher levels of H3K9 acetylation and p21 protein expression. TB and VA-treated rats exhibited increased hepatic concentrations of butyric acid and retinoids, respectively. Compared to normal rats, diethylnitrosamine control animals exhibited lower retinyl palmitate hepatic concentrations. All groups had similar expression levels and exhibited similar unmethylated CRBP-I promoter region in microdissected pPNL, indicating that epigenetic silencing of this gene was not involved in alteration of retinol metabolism in early hepatocarcinogenesis. Data support the effectiveness of TB as a dietary histone deacetylase inhibitor during the promotion phase of hepatocarcinogenesis, which should be considered for chemoprevention combination strategies.
authors.affiliation: Laboratory of Diet, Nutrition and Cancer, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Aline
authors.initials: A
authors.lastname: de Conti
authors.forename: Joice
authors.initials: J
authors.lastname: Kuroiwa-Trzmielina
authors.forename: Maria A
authors.initials: MA
authors.lastname: Horst
authors.forename: Bruna K
authors.initials: BK
authors.lastname: Bassoli
authors.forename: Carlos E A
authors.initials: CE
authors.lastname: Chagas
authors.forename: Eduardo
authors.initials: E
authors.lastname: Purgatto
authors.forename: Felicia P
authors.initials: FP
authors.lastname: Cavalher
authors.forename: Anamaria A
authors.initials: AA
authors.lastname: Camargo
authors.forename: Alceu A
authors.initials: AA
authors.lastname: Jordão
authors.forename: Hélio
authors.initials: H
authors.lastname: Vannucchi
authors.forename: Clarissa
authors.initials: C
authors.lastname: Scolastici
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Ong
authors.forename: Fernando S
authors.initials: FS
authors.lastname: Moreno
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis; D049109:Cell Proliferation; D018890:Chemoprevention; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008114:Liver Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D008297:Male; D011230:Precancerous Conditions / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D014280:Triglycerides / Q000494:pharmacology*; D014801:Vitamin A / Q000494:pharmacology*; D020741:rho GTP-Binding Proteins / Q000378:metabolism
chemical_list: D016588:Anticarcinogenic Agents; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D014280:Triglycerides; D014801:Vitamin A; D006655:Histone Deacetylases; D020741:rho GTP-Binding Proteins; C005830:tributyrin