Tanshinone IIA Alleviates Pirarubicin-Induced Cytotoxicity in H9c2 Cardiomyocytes via Regulation of Hippo Signaling Pathway

Abstract

Malignant tumor is considered as one of the fatal diseases worldwide with high incidence and mortality. Pirarubicin (THP) is an anti-cancer drug commonly used in the treatment of patients with malignancies. In view of that THP exists the cardiotoxic effects, its clinical application is restricted. Tanshinone IIA (TSA) is a core active monomer drawn from Salvia miltiorrhiza that possesses the cardioprotective properties. In the present study, we proposed to unveil the potential and latent mechanism of TSA in the cardiotoxicity caused by THP. Our results validated that THP treatment gave rise to the injury of cardiomyocytes. Moreover, administration of TSA abrogated the impacts of THP on H9c2 cells. A myriad of literatures demonstrate that Hippo pathway plays a critical role in the development of multiple cardiovascular disorders. Hence, we further explored the relationship between TSA and Hippo pathway. It was proven that THP contributed to the activation of Hippo pathway and TSA treatment inhibited Hippo pathway. More importantly, we revealed that TSA attenuated THP-mediated cytotoxicity in cardiomyocytes through modulating Hippo pathway, which provide insights into the improvement of THP-induced toxic and side effects.