The correlation between telomerase activity and Bax/Bcl-2 ratio in valproic acid-treated MCF-7 breast cancer cell line.
OBJECTIVE
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-7 cancer cells. In particular, we investigated VPA effects on viability, apoptosis and telomerase activity.


METHODS
Cytotoxicity effects of VPA on MCF-7 cells were determined by neutral red uptake assay. Cells were treated with different concentrations of VPA (0-32 mM) and telomerase activity and Bax and Bcl-2 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-7 cells were observed as a reduction in cell viability and telomerase activity and altered expression of Bcl-2 family protein levels. The results also showed that there is a significant correlation between reduction of telomerase activity and increase in Bax/Bcl-2 ratio (P=0.001).


CONCLUSIONS
Our study demonstrated that cell viability of MCF-7 cells was decreased after treatment with VPA, probably through a reduction of telomerase activity and an increase in Bax/bcl-2 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.
Department of Biochemistry and Biophysics, Disorder Metabolic Research Center, Golestan University of Medical Sciences, Gorgan, Iran.
Zahra
Z
Vafaiyan
Department of Biochemistry and Biophysics, Disorder Metabolic Research Center, Golestan University of Medical Sciences, Gorgan, Iran.
Roghaye
R
Gharaei
Department of Biochemistry and Biophysics, Disorder Metabolic Research Center, Golestan University of Medical Sciences, Gorgan, Iran.
Jahanbakhsh
J
Asadi
Bax; Bcl-2; MCF-7; Telomerase; Valproic acid