The Effect of Sodium Butyrate on Expression of Androgen Receptor Coregulators and on Prostate Cancer Cell Survival

Background: The androgen receptor (AR) is a member of the nuclear receptor (NR) superfamily. It forms functional transcriptional complexes with multiple coregulatory proteins. Coregulators play significant roles in the AR-mediated growth and progression of prostate cancer cells. Generally, coactivators enhance and coregulators reduce the transcription activity of NRs. Examples of important AR coregulators are nuclear corepressor SMRT (silencing mediator for retinoid and thyroid hormone receptors) and coactivator p300.

It is known that between corepressors and coactivators, there is competition for binding to the AR in the presence of ligands. The change in coregulator expression is important for prostate cancer cell survival. AR interaction with complexes that include SMRT leads to blocking binding coactivators to the AR and inhibition of the transactivation function of the AR.

Sodium butyrate (NaB) as a histone deacetylase inhibitor (HDACI) can alter the acetylation of histones followed by changing the expression of a number of genes.

Methods: In this study we used LNCaP and C4-2 prostate cancer cell lines. As a control cell line was used non-tumorigenic prostate cell line RWPE-1. To investigate the effect of NaB on expression of SMRT and p300, we used RT real-time PCR. The effect of NaB on cell survival was assessed by MTT assay.

Results: Compared with RWPE-1 cell line, in LNCaP and C4-2 cell lines treated with NaB for 24 hours, we found the same level of increased expression of both coregulators SMRT and p300. Decrease in cell viability was weak. In contrast, 48 hours treatment with NaB was followed again by increased expression of SMRT and p300 - but the level of SMRT expression was almost double that of p300. There was significantly visible decrease in cell viability.

Conclusion: NaB has a clear effect on expression of androgen receptor coregulators and as well on prostate cancer cell survival.

This study was supported in part by IGA NS10262-3/2009 and by GAČR 303/09/H048.