Zahra Vafaiyan - Department of Biochemistry and Biophysics, Disorder Metabolic Research Center, Golestan University of Medical Sciences, Gorgan, Iran
Roghaye Gharaei - Department of Biochemistry and Biophysics, Disorder Metabolic Research Center, Golestan University of Medical Sciences, Gorgan, Iran
Jahanbakhsh Asadi - Department of Biochemistry and Biophysics, Disorder Metabolic Research Center, Golestan University of Medical Sciences, Gorgan, Iran

Objective(s):Valproic acid (VPA), a drug used in the treatment of neurological disorders, has been shown to have cytotoxic effects on cancer cells through different mechanisms. Telomerase, a ribonucleoprotein reverse transcriptase, is responsible for elongation of the telomere and is activated in cancers. A relation between telomerase activity and resistance to apoptosis has been established. This study focused on probable effects of VPA on MCF-۷ cancer cells. In particular, we investigated VPA effects on viability, apoptosis and telomerase activity. Materials and Methods: Cytotoxicity effects of VPA on MCF-۷ cells were determined by neutral red uptake assay. Cells were treated with different concentrations of VPA (۰-۳۲ mM) and telomerase activity and Bax and Bcl-۲ protein levels were determined using TRAP assay (PCR-ELISA) method and ELISA method, respectively. Results: The cytotoxic effects of different concentration of VPA on MCF-۷ cells were observed as a reduction in cell viability and telomerase activity and altered expression of Bcl-۲ family protein levels. The results also showed that there is a significant correlation between reduction of telomerase activity and increase in Bax/Bcl-۲ ratio (P=۰.۰۰۱). Conclusion: Our study demonstrated that cell viability of MCF-۷ cells was decreased after treatment with VPA, probably through a reduction of telomerase activity and an increase in Bax/bcl-۲ ratio. Therefore, it could be concluded that VPA is a potent anti-cancer agent for breast cancer cells through inhibition of telomerase activity and induction of apoptosis.

Bax, Bcl-۲, MCF-۷, Telomerase, Valproic acid