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蒽环类药物诱导的心脏毒性中线粒体质量控制的新见解:分子机制、治疗靶点和天然产物。

New insights into mitochondrial quality control in anthracycline-induced cardiotoxicity: molecular mechanisms, therapeutic targets, and natural products.

作者信息

Li Weili, Zhang Yuqin, Wei Yan, Ling Guanjing, Zhang Yawen, Li Yilin, Guo Shujuan, Tan Nannan, Ma Lin, Li Wei, Sun Qianbin, Wang Wei, Wang Yong

机构信息

School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China.

Anhui University of Traditional Chinese Medicine, Anhui 230012, China.

出版信息

Int J Biol Sci. 2025 Jan 1;21(2):507-523. doi: 10.7150/ijbs.103810. eCollection 2025.

Abstract

Anthracyclines (ANTs) are widely used in cancer therapy, particularly for lymphoma, sarcoma, breast cancer, and childhood leukemia, and have become the cornerstone of chemotherapy for various malignancies. However, it is associated with fatal and dose-dependent cardiovascular complications, especially cardiotoxicity. Mitochondrial quality control mechanisms, encompassing mitophagy, mitochondrial dynamics, and mitochondrial biogenesis, maintain mitochondrial homeostasis in the cardiovascular system. Recent studies have highlighted that mitochondrial quality control mechanisms play considerable roles in ANTs-induced cardiotoxicity (AIC). In addition, natural products targeting mitochondrial quality control mechanisms have emerged as potential therapeutic strategies to alleviate AIC. This review summarizes the types, incidence, prevention, treatment, and pathomechanism of AIC, delves into the molecular mechanisms of mitochondrial quality control in the pathogenesis of AIC, and explores natural products that target these mechanisms, so as to provide potential targets and therapeutic drugs for address the clinical challenges in AIC prevention and treatment, where no effective medicines are available.

摘要

蒽环类药物(ANTs)广泛应用于癌症治疗,尤其用于淋巴瘤、肉瘤、乳腺癌和儿童白血病,已成为各种恶性肿瘤化疗的基石。然而,它与致命的、剂量依赖性的心血管并发症相关,尤其是心脏毒性。线粒体质量控制机制,包括线粒体自噬、线粒体动力学和线粒体生物发生,维持心血管系统中的线粒体稳态。最近的研究强调,线粒体质量控制机制在蒽环类药物诱导的心脏毒性(AIC)中起重要作用。此外,针对线粒体质量控制机制的天然产物已成为减轻AIC的潜在治疗策略。本综述总结了AIC的类型、发生率、预防、治疗和发病机制,深入探讨了线粒体质量控制在AIC发病机制中的分子机制,并探索了针对这些机制的天然产物,以便为解决AIC预防和治疗中的临床挑战提供潜在靶点和治疗药物,目前尚无有效的药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a4a/11705644/497914d17b68/ijbsv21p0507g001.jpg

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