Effect of valproic acid on JAK/STAT pathway, SOCS1, SOCS3, Bcl-xL, c-Myc, and Mcl-1 gene expression, cell growth inhibition and apoptosis induction in human colon cancer HT29 cell line.

Background and aim: Cytokines are a large family of protein messengers. These proteins induce various cellular responses. Janus kinases (JAKs) are mediators of cytokine, activated JAKs phosphorylate signal transducers, and activators of transcription (STAT) proteins that regulate cell differentiation, proliferation, and apoptosis. Aberrant JAK/STAT signaling is involved in the oncogenesis of several cancers. Aberrant STAT promotes uncontrolled cell growth through dysregulation of target genes including Bcl-xL, c-Myc, Mcl-1, CCND1, and VEGF, and thereby contributes to oncogenesis. Epigenetic silencing and downregulation of SOCSs activates JAK‐STAT signaling and cancer induction [7]. It has been reported that histone deacetylase inhibitors (HDACs) such as trichostatin A (TSA) increases the acetylation of histones associated with the suppressors of cytokine signaling (SOCS) geneS promoters resulting in the gene reactivation and apoptosis induction in colorectal. The current study aimed to investigate the effect of VPA on JAK1, JAK2, STAT3, STAT5A, STAT5B, SOCS1, SOCS3, Bcl-xL, c-Myc, and Mcl-1 gene expression, cell growth inhibition, and apoptosis induction in human colon cancer HT29 cell line. Materials and Methods: The HT29 cells were treated with VPA. To determine cell viability, cell apoptosis, and gene expression, MTT assay, flow cytometry, and Real-time quantitative RT-PCR (qRT-PCR) were done respectively. Results: VPA inhibited cell viability, induced apoptosis, down-regulated JAK1, JAK2, STAT3, STAT5A, STAT5B, Bcl-xL, c-Myc, and Mcl-1 and up-regulated SOCS1 and SOCS3 significantly. Conclusion: VPA can induce apoptosis in colon cancer HT29 cell line through JAK/STAT pathway.