The mechanism and therapeutic strategies in doxorubicin-induced cardiotoxicity: Role of programmed cell death

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Cell Stress & Chaperones Pub Date : 2024-10-01 DOI:10.1016/j.cstres.2024.09.001

Yanzhao Li , Jing Yan , Pingzhen Yang

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引用次数: 0

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 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.

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多柔比星诱发心脏毒性的机制和治疗策略：程序性细胞死亡的作用

多柔比星（DOX）是最常用的蒽环类抗癌药，但其临床应用却受到心脏毒性等有害副作用的限制。大量研究表明，程序性细胞死亡在多柔比星诱导的心脏毒性（DIC）中扮演着重要角色。本综述总结了几种程序性细胞死亡，包括细胞凋亡、热凋亡、坏死、自噬和铁凋亡。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，本综述阐明了相关的信号通路，包括 SIRT1/Nrf2、SIRT1/Klotho、SIRT1/SESN2、AMPK、AKT 和 PPAR。热休克蛋白具有伴侣蛋白的功能，在各种应激情况下发挥着重要作用，尤其是在心脏中。因此，一些与 DIC 有关的热休克蛋白也包括在内。因此，本综述的最后一部分将重点讨论基于上述机制的治疗研究。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell Stress & Chaperones 生物-细胞生物学

CiteScore

7.60

自引率

2.60%

发文量

审稿时长

6-12 weeks

期刊介绍： Cell Stress and Chaperones is an integrative journal that bridges the gap between laboratory model systems and natural populations. The journal captures the eclectic spirit of the cellular stress response field in a single, concentrated source of current information. Major emphasis is placed on the effects of climate change on individual species in the natural environment and their capacity to adapt. This emphasis expands our focus on stress biology and medicine by linking climate change effects to research on cellular stress responses of animals, micro-organisms and plants.