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11, 25 dihydroxy vitamin D3, an active metabolite of vitamin­D3 has been reported to inhibit the growth of number neoplasms such as prostate, breast, colorectal, leukemia and skin cancers. Valproic acid, as a potent histone deacetylase inhibitor, also plays an important role in inhibition of proliferation of tumor cells. However, there are no reports so far on the cooperation between valproic acid and vitamin­ D3 for anti-leukemic effect. The goal of the present research was to evaluate whether low doses of vitamin D3 potentiate the toxicity of valproic acid and whether this toxic action is mediated via apoptotic mechanisms. In this study HL-60 cells were treated either with different concentrations of valproic acid and vitamin­ D3 alone and in combination with each other for 24 hours. Cell survival was determined by MTT assay and then Hoechst staining was used to determine the type of death cell. This present study indicates that vitamin ­D3 potentiates the antitumor effects of valproic acid. Also, the results of staining cells showed that valproic acid and vitamin ­D3 induced apoptosis in HL-60 cells. In total, the new combination of valproic acid and vitamin D3 showed synergistic anti-proliferative effect and induced apoptosis on HL-60 cancer cells.
                                                                       

Keywords: Acute promyelocytic leukemia, anti-proliferation, apoptosis, differentiation, histone deacetylase inhibitor

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