Abstract 2152: The influence of didox on the efficacy and toxicity of doxorubicin.

Abstract

Abstract Didox, possess antioxidant propertieson the top of its DNA synthesis and repair inhibiting ability. Doxorubicin (DOX) is a major chemotherapy for liver cancer; however it evokes severe cardiotoxic effect which is attributed to DOX derived free radicals. Herein, we assessed the effect didox in enhancing DOX efficacy in liver cancer cells while protecting against its cardiotoxic effects. Combination with didox significantly reduced in the IC50 of DOX in Huh7 and HepG2 liver cancer cell lines. The combination index between DOX and didox indicated additive type interaction (CI-value of 0.81-0.9). Both DOX and didox significantly blocked the cell cycle in S-phase and their combination significantly aggravated that block. In addition, didox with DOX showed higher caspase-3 level compared to DOX alone. This enhancement effect might be attributed to didox induced PARP enzyme inhibition. On the other hand, didox (150 mg/kg daily) significantly protected the cardiomyocyte and decreased the intra cardiac reactive oxygen species induced by DOX treatment (15 mg/kg). This effect was coupled with reverting DOX induced cardiomegaly and cardio-pathological features. Didox significantly prolonged the median survival of DOX treated mice and reduced their mortality risk by 3.7 folds. In conclusion, didox significantly improved the cytotoxic effect of DOX in liver cancer cells and protected from its cardiotoxic side effects. Citation Format: Fahad A. Al-Abbasi, Gihan F. Assad, Ahmed M. Al-Abd, Ashraf B. Abdel-Naim. The influence of didox on the efficacy and toxicity of doxorubicin. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2152. doi:10.1158/1538-7445.AM2013-2152