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

• Published in: The Journal of nutritional biochemistry 2012-08, Vol.23 (8), p.860-866
• Main Authors: de Conti, Aline, Kuroiwa-Trzmielina, Joice, Horst, Maria A, Bassoli, Bruna K, Chagas, Carlos E.A, Purgatto, Eduardo, Cavalher, Felicia P, Camargo, Anamaria A, Jordão, Alceu A. Jr, Vannucchi, Hélio, Scolastici, Clarissa, Ong, Thomas P, Moreno, Fernando S
• Format: Article
• Language: English
• Subjects: acetylation; Animals; Anticarcinogenic Agents - pharmacology; Apoptosis; Biological and medical sciences; butyric acid; Cell Proliferation; Chemoprevention; Epigenetic; Feeding. Feeding behavior; Fundamental and applied biological sciences. Psychology; gene silencing; Hepatocarcinogenesis; Hepatocytes - metabolism; Hepatocytes - pathology; histone deacetylase; Histone Deacetylase Inhibitors - pharmacology; Histone Deacetylases - metabolism; Histones - metabolism; Liver - metabolism; Liver - pathology; Liver Neoplasms, Experimental - metabolism; Liver Neoplasms, Experimental - pathology; Liver Neoplasms, Experimental - prevention & control; Male; Precancerous Conditions - metabolism; Precancerous Conditions - pathology; Precancerous Conditions - prevention & control; promoter regions; protein synthesis; Rats; Rats, Wistar; retinyl palmitate; rho GTP-Binding Proteins - metabolism; Tributyrin; Triglycerides - pharmacology; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vitamin A; Vitamin A - pharmacology
• ISSN: 0955-2863; 1873-4847
• DOI: 10.1016/j.jnutbio.2011.04.010

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.