Effects of combination treatment using arsenic trioxide and resveratrol on human breast cancer (MCF-7) cells

Abstract Background: Arsenic trioxide (ATO) has shown remarkable efficacy in the treatment of cancer. Resveratrol (RSV) has anti-tumor, anti-aging, and anti-inflammatory properties. We examined the anti-cancer effects of using ATO plus RSV together against human breast cancer (MCF-7) cells.Methods: MCF-7 cells were treated with ATO (0–16 μM) alone or combined with RSV (0–100 μM). Cell viability and percent apoptosis were estimated using Cell Counting Kit-8, the TUNEL assay and microscopy. mRNA and protein expression of caspase-3, caspase-7, Bax, and B-cell lymphoma (Bcl)-2 were assessed by real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting. Chromatin immunoprecipitation (ChIP) was adopted to determine the histone acetylation of the promoter regions of caspase-3, caspase-7, Bax, and Bcl-2.Results: Combined treatment was more efficacious than treatment of ATO alone or RSV alone in suppressing the viability of MCF-7 cells. The intracellular mechanisms of cytotoxicity of ATO+RSV treatment were revealed to be a relative increase in mRNA and protein expression of caspase-3, caspase-7, and Bax, and relative decrease in Bcl-2, in MCF-7 cells. ChIP results showed that combined treatment increased the acetylation of histone H3K27 in the promoter region of caspase-3, caspase-7, and Bax, but decreased the acetylation of histone H3K27 in Bcl-2.Conclusion: Combination therapy using ATO and RSV could be employed for BC treatment.