Expression of miR-125 and MCL-1 and BCL-2 Anti-apoptotic Genes under the Influence of Valproic Acid Treatment in Breast Cancer Cell Lines

One of the causes of death through breast cancer is drug resistance and the anti-apoptotic activity of cancer cells. Epigenetic factors are involved in both of these processes. Micro RNAs (miRNAs) are epigenetic agents that accelerate the inappropriate expression of cancer. Valproic acid is a histone deacetylase inhibitor that has anticancer activity. The aim of this study was to evaluate the effect of valproic acid on miR-125b expression as one of the tumor suppressor miRNAs in breast cancer, and the expression of BCL-2 and MCL-1 anti-apoptotic genes as possible targets of miR-125b in MDA-MB-231 and MCF-7 cell lines.

In this experimental study, MDA-MB-231 and MCF-7 cell lines were first cultured in optimal conditions. Cell viability was measured at different concentrations of valproic acid at 48 and 72 hours using MTT assay. The expression of miR-125b and BCL-2 and MCL-1 genes was analyzed using real-time polymerase chain reaction (PCR). The data were analyzed using one-way ANOVA test.

Valproic acid significantly decreased the viability of both cell lines in dose- and time-dependent manner. It also led to a significant increase in miR-125b in both cell lines (P < 0.010). In MCF-7 cells, this drug led to a significant decrease in BCL-2 and MCL-1 genes (P < 0.001). But the difference in these two genes in MDA-MB-231 treated cells was not significant compared to the control group (P > 0.050).

Valproic acid may be suggested as a profitable option in cancer research, through its involvement in epigenetic processes, and its influence on the expression of BCL-2 and MCL-1 genes.