the correlation between telomerase activity and bax/bcl-2 ratio in valproic acid-treated mcf-7 breast cancer cell line
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abstract
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-7 cancer cells. in particular, we investigated vpa effects on viability, apoptosis and telomerase activity. materials and 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). conclusion: 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.
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Journal title:
iranian journal of basic medical sciencesجلد ۱۸، شماره ۷، صفحات ۷۰۰-۷۰۴
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