The use of adjuvant
therapies in
cancer treatment is rationalized by potentiating the efficacy and/or protecting from the major side effects of chemotherapeutics.
Didox, besides its
antioxidant properties, is an inhibitor for
DNA synthesis and repair which might recommend its use as adjuvant
therapy. Herein, we have studied the effect of
didox in potentiating the efficacy of
doxorubicin (DOX) against
liver cancer cells and protecting from its dose-limiting cardiotoxic effects.
Didox combination with DOX significantly decreased in the IC50 of DOX to half its original value in Huh7 and HepG2
liver cancer cell lines. The calculated combination index (CI-value) indicated additive type of drug interaction (CI-value ranged from 0.81 to 0.9). Both
didox and DOX significantly blocked the cell cycle in S-phase and their combination significantly increased cell cycle blockade. Also,
didox combination significantly increase the
caspase-3 level compared to DOX treatment alone. On the other hand,
didox (150 mg/kg daily) significantly protected the cardiomyocyte membrane integrity and decreased the intra-cardiac oxidative stress induced by DOX treatment (15 mg/kg). This protective effect was reflected in reverting the
cardiomegaly and cardio-pathological features induced by DOX treatment. Also
didox prolonged the median survival time of mice treated with DOX and decreased the mortality risk by 3.7 folds. In conclusion,
didox significantly potentiated the cytotoxicity of DOX in
liver cancer cells and protected from its
cardiotoxicity.