Effects of trichostatin A on FHIT and WWOX genes expression, cell growth inhibition and apoptosis induction in hepatocellular carcinoma WCH 17 cell line

Abstract

Previously, we evaluated the effect of trichostatin A (TSA) on the expression of DNA methyltransferase 1 (DNMT1) in Hepatocellular Carcinoma (HCC). Fragile histidine triad (FHIT) and WW domaincontaining oxidoreductase (WWOX) are two of the most common down-regulated genes in many cancers located on chromosome 3p14.2 and 16q23.3-24.1 respectively. The aim of the current study was to assess the effect of TSA on these genes expression, cell growth, and apoptosis in HCC WCH 17 cell. The cells were seeded and treated with TSA at different times. Then, MTT assay, flow cytometry, and qRT-PCR were achieved to determine viability, apoptosis and gene expression respectively. Cell growth was significantly inhibited, 92 to 36% after 24 h, 86 to 28% after 48 h, and 78 to 24% after 72 h. The results of flow cytometry confirmed that TSA increased apoptosis compared to the control group, the apoptosis percentage increased to 12%, 16%, and 18% in comparison to control groups (2%). Significant up-regulation of the genes was observed in all treated groups. We concluded that reexpression of silenced WWOX and FHIT genes could be achieved by TSA resulting in cell growth inhibition and apoptosis induction in WCH 17 cell.

Valproic Acid Treatment Enhances Chromosome Flexibility and Electron Transport in MCF7 Breast Cancer Cells

“…In MCF7 cell, VPA was reported to induce apoptosis at the lowest dose of 0.5mM after 8 days of treatment 36 . In a similar study, Masumeh et al reported a VPA -IC50 value of 3µM 21 . Earlier reports also found morphological changes in MCF7 cells after exposure to VPA for more than 48 hrs 16 .…”

“…reported a VPA -IC50 value of 3µM 21 . Earlier reports also found morphological changes in MCF7 cells after exposure to VPA for more than 48 hrs 16 .…”

“…Therefore, VPA induces chromatin structural rearrangements through epigenetic reprogramming involving demethylation and acetylation of specific genes/histones 20 . Previous biochemical studies revealed that VPA prompts chromatin decondensation, repair of damaged DNA, cell differentiation, apoptosis (by upregulation of Bak, downregulation of Bcl-2 expression ), and cell cycle arrest (G1 or sub-G1 phases ) in BC 12,16,[20][21][22] . Presently this compound is of great interest to the field and is undergoing many clinical trials for its anti-proliferative properties in a variety of cancer types including BC 12 .…”