Research progress on the role and mechanism of Sirtuin family in doxorubicin cardiotoxicity

Xuan Zhang; Chaoming Huang; Yanhong Hou; Shisheng Jiang; Yu Zhang; Shulin Wang; Jiamin Chen; Jianmei Lai; Lifeng Wu; Huiying Duan; Shuwen He; Xinyi Liu; Shanshan Yu; Yi Cai

doi:10.1016/j.phymed.2024.155673

Research progress on the role and mechanism of Sirtuin family in doxorubicin cardiotoxicity

Phytomedicine. 2024 Apr 22:129:155673. doi: 10.1016/j.phymed.2024.155673. Online ahead of print.

Authors

Xuan Zhang¹, Chaoming Huang¹, Yanhong Hou¹, Shisheng Jiang¹, Yu Zhang¹, Shulin Wang², Jiamin Chen¹, Jianmei Lai¹, Lifeng Wu¹, Huiying Duan¹, Shuwen He¹, Xinyi Liu¹, Shanshan Yu³, Yi Cai⁴

Affiliations

¹ Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou 511436, China.
² The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Guangzhou Medical University, Guangzhou, Qingyuan 511500, China.
³ Department of Pharmacy, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China. Electronic address: hygeia1019@163.com.
⁴ Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou 511436, China. Electronic address: yicaisysu@163.com.

PMID: 38677274
DOI: 10.1016/j.phymed.2024.155673

Abstract

Background: Doxorubicin (DOX) is a widely utilized anthracycline chemotherapy drug in cancer treatment, yet its efficacy is hindered by both short-term and long-term cardiotoxicity. Although oxidative stress, inflammation and mitochondrial dysfunction are established factors in DOX-induced cardiotoxicity, the precise molecular pathways remain elusive. Further exploration of the pathogenesis and identification of novel molecular targets are imperative. Recent studies have implicated the Sirtuins family in various physiological and pathological processes, suggesting their potential in ameliorating DOX-induced cardiotoxicity. Moreover, research on Sirtuins has discovered small-molecule compounds or medicinal plants with regulatory effects, representing a notable advancement in preventing and treating DOX-induced cardiac injury.

Purpose: In this review, we delve into the pathogenesis of DOX-induced cardiotoxicity and explore the therapeutic effects of Sirtuins in mitigating this condition, along with the associated molecular mechanisms. Furthermore, we delineate the roles and mechanisms of small-molecule regulators of Sirtuins in the prevention and treatment of DOX-induced cardiotoxicity.

Study-design/methods: Data for this review were sourced from various scientific databases (such as Web of Science, PubMed and Science Direct) up to March 2024. Search terms included "Sirtuins," "DOX-induced cardiotoxicity," "DOX," "Sirtuins regulators," "histone deacetylation," among others, as well as several combinations thereof.

Results: Members of the Sirtuins family regulate both the onset and progression of DOX-induced cardiotoxicity through anti-inflammatory, antioxidative stress and anti-apoptotic mechanisms, as well as by maintaining mitochondrial stability. Moreover, natural plant-derived active compounds such as Resveratrol (RES), curcumin, berberine, along with synthetic small-molecule compounds like EX527, modulate the expression and activity of Sirtuins.

Conclusion: The therapeutic role of the Sirtuins family in mitigating DOX-induced cardiotoxicity represents a potential molecular target. However, further research is urgently needed to elucidate the relevant molecular mechanisms and to assess the safety and biological activity of Sirtuins regulators. This review offers an in-depth understanding of the therapeutic role of the Sirtuins family in mitigating DOX-induced cardiotoxicity, providing a preliminary basis for the clinical application of Sirtuins regulators in this condition.

Keywords: Apoptosis; Cardiotoxicity; Doxorubicin; Oxidative stress; Sirtuins.