Abstract:
Acetaminophen (APAP) is widely used to treat pain and to reduce fever, while APAP overdose causes hepatic centrilobular necrosis. Recent studies have reported that APAP alone or combined with chemotherapy inhibited cell proliferation in various cancer cells and xenografts. However, anticancer effects of APAP combined with radiotherapy are still unclear. The present study investigated whether APAP combined with radiation would enhance the anticancer effects of radiation alone in MDA-MB-231 breast cancer cell line, focusing on cell cycle regulation. APAP inhibited clonogenic cell survival and induced morphological changes in a dose-dependent manner (0~20 mM). Low dose-APAP (2 mM, survival fraction: 0.89) enhanced the radio-sensitivity of MDA-MB-231 cancer cells. In addition, combination of low-dose APAP and radiation blocked radiation-induced G2/M arrest and reduced expression of cyclinB1 protein, which is G2/M checkpoint regulator, in MDA-MB-231 cancer cells. Our results showed that low-dose APAP enhanced radio-sensitizing effect by regulating cell cycle progression. Further research is needed that APAP toxicity is assessed by production of APAP-induced toxic metabolites using LC-MS/MS analysis and then radio-sensitivity of nontoxic dose APAP is identified in MDA-MB-231 xenograft mice.
