Chemopreventive effects of the dietary histone deacetylase inhibitor tributyrin alone or in combination with vitamin A during the promotion phase of rat hepatocarcinogenesis

Author(s):Show less -

de Conti, Aline ; Kuroiwa-Trzmielina, Joice ; Horst, Maria A. ; Bassoli, Bruna K. ; Chagas, Carlos E. A. ; Purgatto, Eduardo ^[1] ; Cavalher, Felicia P. ^[2] ; Camargo, Anamaria A. ^[2] ; Jordao, Jr., Alceu A. ^[3] ; Vannucchi, Helio ^[3] ; Scolastici, Clarissa ; Ong, Thomas P. ; Moreno, Fernando S. ^[4]

Affiliation

^[1] Univ Sao Paulo, Dept Food & Expt Nutr, Fac Pharmaceut Sci, Lab Food Chem & Biochem, BR-05508900 Sao Paulo - Brazil

^[2] Ludwig Inst Canc Res, Lab Mol Biol & Genom, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Clin Med, Div Nutr, Ribeirao Preto, SP - Brazil

^[4] Univ Sao Paulo, Dept Alimentos Nutr Expt, Fac Ciencias Farmaceut, Lab Diet Nutr & Canc, BR-05508900 Sao Paulo - Brazil

• Document type: Journal article
• Source: JOURNAL OF NUTRITIONAL BIOCHEMISTRY; v. 23, n. 8, p. 860-866, AUG 2012.
• Web of Science Citations: 9

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. (C) 2012 Elsevier Inc. All rights reserved. (AU)