Department of Second Clinical Medical College, Southern Medical University, Guangzhou, China.
Department of Cardiology, Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Cell Stress Chaperones. 2024 Oct;29(5):666-680. doi: 10.1016/j.cstres.2024.09.001. Epub 2024 Sep 27.
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 programmed cell death plays a significant role in DOX-induced cardiotoxicity (DIC). This review summarizes several kinds of programmed cell death, including apoptosis, pyroptosis, necroptosis, autophagy, and ferroptosis. Furthermore, oxidative stress, inflammation, and mitochondrial dysfunction are also important factors in the molecular mechanisms of DIC. Besides, a comprehensive understanding of specific signal pathways of DIC can be helpful to its treatment. Therefore, the related signal pathways are elucidated in this review, including sirtuin deacetylase (silent information regulator 2 [Sir2]) 1 (SIRT1)/nuclear factor erythroid 2-related factor 2, SIRT1/Klotho, SIRT1/Recombinant Sestrin 2, adenosine monophosphate-activated protein kinase, AKT, and peroxisome proliferator-activated receptor. Heat shock proteins function as chaperones, which play an 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.
多柔比星（DOX）是最常用的蒽环类抗癌药物，但其临床应用受到心脏毒性等有害副作用的限制。大量研究表明，程序性细胞死亡在 DOX 诱导的心脏毒性（DIC）中起着重要作用。本综述总结了几种程序性细胞死亡，包括细胞凋亡、细胞焦亡、细胞坏死、自噬和铁死亡。此外，氧化应激、炎症和线粒体功能障碍也是 DIC 分子机制中的重要因素。此外，全面了解 DIC 的特定信号通路有助于其治疗。因此，本综述阐述了相关信号通路，包括沉默信息调节因子 2 相关酶 1（Sir2）/核因子红细胞 2 相关因子 2、SIRT1/Klotho、SIRT1/重组 Sestrin 2、单磷酸腺苷激活蛋白激酶、AKT 和过氧化物酶体增殖物激活受体。热休克蛋白作为伴侣发挥作用，在各种应激情况下，特别是在心脏中发挥重要作用。因此，DIC 中涉及的一些热休克蛋白也包括在内。因此，本综述的最后一部分重点介绍了基于上述机制的治疗研究。
