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

Brazilian Journal of Medical and Biological Research

F.o. Andrade²  M.k. Nagamine¹  A. De Conti²  L.m. Chaible¹  C.c. Fontelles²  A.a. Jordão Junior¹  H. Vannucchi¹  M.l.z. Dagli¹  B.k. Bassoli²  F.s. Moreno²  T.p. Ong² 

[1] ,Universidade de São Paulo Faculdade de Ciências Farmacêuticas Departamento de Alimentos e Nutrição ExperimentalSão Paulo SP ,Brasil

关键词: Breast cancer;    MCF-7 cells;    Butyric acid;    Vitamin A;    Epigenetics;   

DOI  :  10.1590/S0100-879X2012007500103

来源: SciELO

【 摘 要 】

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.

【 授权许可】

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