Anthocyanins confer cardioprotection against Doxorubicin by modulating the AMPK-SIRT1-p53 pathway

Doxorubicin (Doxo) is one of the most effective chemotherapeutic drugs, but its clinical use is severely limited by its side effects, leading to cardiomyopathy and heart failure. An anthocyanin (ACN)-rich diet from purple corn (RED diet), which mainly contains cyanidin 3-glucoside (C3G) and its acetylated derivatives, was proved to be effective in reducing Doxo-induced cardiotoxicity in mice. Aiming at unveiling the molecular mechanisms involved in ACN protection, we decided to consider the AMPK-SIRT1-p53 pathway that recently gained interest for its cardioprotective role. HL-1 murine cardiomyocytes were treated with Doxo in presence or absence of purple corn extract (RED) and activation level of AMPK, SIRT1, p53 and its apoptosis-related target genes were evaluated. Our results showed that RED decreased Doxo-induced AMPK activation and increased p53 acetylation, which resulted in decreased levels of cleaved-Caspase 3, Puma and p21 transcripts and apoptosis. The RED-induced p53 acetylation and its cardioprotective role is currently under validation in mouse primary cardiomyocytes. In conclusion, RED may prevent cardiomyocytes apoptosis through AMPK and SIRT1 modulation.