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

Abstract

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 104 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.

Critical Dietary Factors in Cancer Chemoprevention

“…Subsequently, RA modulates transcription through its response elements in the promoters of target genes, including p21 and AP-1, and exerts the pro-apoptotic actions (Stefanska et al 2012a). In the combined treatment, butyrate and RA inhibited proliferation of MCF-7 cells (Andrade et al 2012). In the combined treatment, butyrate and RA inhibited proliferation of MCF-7 cells (Andrade et al 2012).…”

Global histone post-translational modifications and cancer: Biomarkers for diagnosis, prognosis and treatment?

“…The same group also reported that the combination of HDACi entinostat with the DNMTi azacitidine was able to decrease tumor size and reduce the growth of K-ras/p53 mutant lung adenocarcinomas orthotopic engrafted in immunocompromised nude rats [127] . In another case HDACi sodium butyrate reduces the cell proliferation of MCF-7 cell when combine with vitamin-A [128] .…”

Epigenetic Impact of Bioactive Dietary Compounds in Cancer Chemoprevention

“…It has been demonstrated that the treatment of noninvasive MCF-7 cells with RA caused the decrease in promoter methylation, consequent increase in the RARβ2 and PTEN (phosphatase and tensin homologue) expression, and the inhibition of breast cancer cell growth (Stefanska et al 2012b). In the combined treatment, butyrate and RA inhibited proliferation of MCF-7 cells (Andrade et al 2012). Thus, retinoids have been suggested as a potential epigenetic strategy for the cancer treatment, especially in breast cancers in which RAR β is epigenetically altered.…”