Efficacy of the dietary histone deacetylase inhibitor butyrate alone or in combination with vitamin A against proliferation of MCF-7 human breast cancer cells.
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.
Laboratório de Dieta, Nutrição e Câncer, Departamento de Alimentos e Nutrição Experimental, Universidade de São Paulo, São Paulo, SP, Brasil.
F O
FO
Andrade
M K
MK
Nagamine
A De
AD
Conti
L M
LM
Chaible
C C
CC
Fontelles
A A
AA
Jordão Junior
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H
Vannucchi
M L Z
ML
Dagli
B K
BK
Bassoli
F S
FS
Moreno
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Ong
D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000473:pathology*; D002087:Butyrates / Q000008:administration & dosage / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects*; D019175:DNA Methylation / Q000187:drug effects*; D005260:Female; D056572:Histone Deacetylase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D061986:MCF-7 Cells; D014801:Vitamin A / Q000008:administration & dosage / Q000494:pharmacology*
D016588:Anticarcinogenic Agents; D002087:Butyrates; D056572:Histone Deacetylase Inhibitors; D014801:Vitamin A