Different effect of sodium butyrate on cancer and normal prostate cells

Abstract

Sodium butyrate, as a naturally occurring inhibitor of histone deacetylases (HDACI), is a non-toxic agent, with an ability to change histone acetylation and expression of large number genes.This study shows different effects of sodium butyrate on expression and transcription activity of the androgen receptor in cancer (LNCaP, C4-2) and normal (RWPE-1) prostate cells. Moreover, we studied the coregulator expressions and histone acetylation alteration in cancer and normal cells. Coregulators, coactivators as well as corepressors, play an important role in AR-mediated growth and progression of prostate cancer. There is a competition between coactivators and corepressors for binding on the AR and therefore the changes in coregulators expression and ratio could be important for prostate cancer survival. Our study was focused on two coregulators, SMRT and p300, which interact with AR in multiprotein complex and affect the AR transcription activity.Our data indicate that sodium butyrate has an effect on AR coregulators expression, transcription activity and histone acetylation in cancer cells, but there is only minimal effect in normal cells. In addition, the results of changes in acetylation level on lysine residues of histone H4 after sodium butyrate treatment confirm its epigenetic effect on prostate cancer cells.