Efficacy of the dietary histone deacetylase inhibitor butyrate alone or in combination with vitamin A against proliferation of MCF-7 human breast cancer cells

• Published in: Brazilian journal of medical and biological research 2012-09, Vol.45 (9), p.841-850
• Main Authors: Andrade, F O, Nagamine, M K, Conti, A De, Chaible, L M, Fontelles, C C, Jordão Junior, A A, Vannucchi, H, Dagli, M L Z, Bassoli, B K, Moreno, F S, Ong, T P
• Format: Article
• Language: English
• Subjects: Anticarcinogenic Agents - administration & dosage; Anticarcinogenic Agents - pharmacology; BIOLOGY; Breast cancer; Breast Neoplasms - pathology; Butyrates - administration & dosage; Butyrates - pharmacology; Butyric acid; Cell Proliferation - drug effects; DNA Methylation - drug effects; Epigenetics; Female; Histone Deacetylase Inhibitors - administration & dosage; Histone Deacetylase Inhibitors - pharmacology; Humans; MCF-7 Cells; MEDICINE, RESEARCH & EXPERIMENTAL; Short Communication; Vitamin A; Vitamin A - administration & dosage; Vitamin A - pharmacology
• ISSN: 0100-879X; 1414-431X; 1414-431X; 0100-879X
• DOI: 10.1590/S0100-879X2012007500103

The combined treatment with histone deacetylase inhibitors (HDACi) and retinoids has been suggested as a potential epigenetic strategy for the control of cancer. In the present study, we investigated the effects of treatment with butyrate, a dietary HDACi, combined with vitamin A on MCF-7 human breast cancer cells. Cell proliferation was evaluated by the crystal violet staining method. MCF-7 cells were plated at 5 x 10(4) cells/mL and treated with butyrate (1 mM) alone or combined with vitamin A (10 µM) for 24 to 120 h. Cell proliferation inhibition was 34, 10 and 46% following treatment with butyrate, vitamin A and their combination, respectively, suggesting that vitamin A potentiated the inhibitory activities of butyrate. Furthermore, exposure to this short-chain fatty acid increased the level of histone H3K9 acetylation by 9.5-fold (Western blot), but not of H4K16, and increased the expression levels of p21WAF1 by 2.7-fold (Western blot) and of RARβ by 2.0-fold (quantitative real-time PCR). Our data show that RARβ may represent a molecular target for butyrate in breast cancer cells. Due to its effectiveness as a dietary HDACi, butyrate should be considered for use in combinatorial strategies with more active retinoids, especially in breast cancers in which RARβ is epigenetically altered.