The mechanism and therapeutic strategies in Doxorubicin induced cardiotoxicity: Role of programmed cell death.

Abstract

Doxorubicin (DOX) is the most commonly used anthracycline anticancer agent, while its clinical utility is limited by harmful side effects like cardiotoxicity. Numerous studies have elucidated that the programmed cell death plays a significant role in doxorubicin induced cardiotoxicity (DIC). This review summarizes several kinds of programmed cell death, including apoptosis, pyroptosis, necroptosis, autophagy and ferroptosis. Furthermore, oxidative stress, inflammation and mitochondial dysfunction, are also important factors in the molecular mechanisms of DIC. Besides, a comprehensive understanding of specific signal pathway of DIC can be helpful to its treatment. Therefore, the related signal pathways are elucidated in this review, including SIRT1/Nrf2, SIRT1/Klotho, SIRT1/SESN2, AMPK, AKT and PPAR. Heat Shock Proteins function as chaperones, which play important role in various stressful situations, especially in the heart. Thus, some of Heat Shock Proteins involved in DIC are also included. Hence, the last part of this review focuses on the therapeutic research based on the mechanisms above.