Effect of sodium butyrate on HDAC8 mRNA expression in colorectal cancer cell lines and molecular docking study of LHX1 - sodium butyrate interaction

Abstract

Colorectal cancer (CRC) is the third common cancer and the fourth leading cause of cancer related death worldwide. Histone Deacetylase 8 (HDAC8) has a unique feature and is a good target for drug design. The LHX1 factor is an important transcription factor for this gene. The aim of this study was to investigate the effect of sodium butyrate (NaB) as a histone deacetylase inhibitors on the expression of the HDAC8 gene in the colorectal cancer cell line, and the molecular docking of LHX1 transcription factor with NaB. HCT-116 and HT-29 cell lines were treated with different concentrations of NaB (6.25mM to 150 mM) at 24, 48 and 72 hours. RNA was extracted from the treated and untreated cells and cDNA was synthesized. Quantitative Real-Time-PCR was done to investigate the mRNA expression of HDAC8. Molecular docking was performed to investigate NaB and LHX1 interaction. On the base of Real-time-PCR results, the concentration of 150 mM NaB after 24 hours in HT-29 and HCT-116 cell lines caused a significant reduction in mRNA expression of HDAC8 (P<0.05). In 48 hours of treatment, there was a significant decrease in the mRNA expression of HDAC8 at all concentrations (P<0.05). The docking results showed that LHX1 and NaB interacted the best way with the lowest energy levels. Our results showed that NaB bond to LHX1 strongly. Our results demonstrated that NaB bind to the LHX1 transcription factor and inhibited the function of this factor and subsequently the transcription from the HDAC8 gene was decreased and results in cell death. Future studies are needed to assess the molecular mechanisms of NaB on gene expression.