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Molecular mechanisms of doxorubicin-induced cardiotoxicity: novel roles of sirtuin 1-mediated signaling pathways

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Abstract

Doxorubicin (DOX) is an anthracycline chemotherapy drug used in the treatment of various types of cancer. However, short-term and long-term cardiotoxicity limits the clinical application of DOX. Currently, dexrazoxane is the only approved treatment by the United States Food and Drug Administration to prevent DOX-induced cardiotoxicity. However, a recent study found that pre-treatment with dexrazoxane could not fully improve myocardial toxicity of DOX. Therefore, further targeted cardioprotective prophylaxis and treatment strategies are an urgent requirement for cancer patients receiving DOX treatment to reduce the occurrence of cardiotoxicity. Accumulating evidence manifested that Sirtuin 1 (SIRT1) could play a crucially protective role in heart diseases. Recently, numerous studies have concentrated on the role of SIRT1 in DOX-induced cardiotoxicity, which might be related to the activity and deacetylation of SIRT1 downstream targets. Therefore, the aim of this review was to summarize the recent advances related to the protective effects, mechanisms, and deficiencies in clinical application of SIRT1 in DOX-induced cardiotoxicity. Also, the pharmaceutical preparations that activate SIRT1 and affect DOX-induced cardiotoxicity have been listed in this review.

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Acknowledgements

This study was supported by Qilu Young Scholar's Program of Shandong University (21330089963007), National Natural Science Foundation of China (81700329, 81770375) and Jilin Science and Technology Department (20200801061GH).

Funding

This study was supported by Qilu Young Scholar’s Program of Shandong University (21330089963007), National Natural Science Foundation of China (81700329, 81770375) and Jilin Science and Technology Department (20200801061GH).

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Authors and Affiliations

  1. School of Nursing, Cheeloo College of Medicine, Shandong University, **an, 250012, Shandong, China

    Jie Wang(a), Mengjie **ao, Jie Wang(b), Yuanfang Guo & Junlian Gu

  2. Department of Cardiology, The First Hospital of China Medical University, Shenyang, 110016, Liaoning, China

    **g**g Zhang

  3. Department of Cardiology, The People’s Hospital of Liaoning Province, Shenyang, 110016, Liaoning, China

    **g**g Zhang

  4. Department of Cardiology, The First Hospital of Jilin University, Changchun, 130021, Jilin, China

    Shudong Wang

  5. Department of Orthopedic Surgery, The First Affiliated Hospital of Shandong First Medical University, **an, 250014, Shandong, China

    Yufeng Tang

Authors
  1. Jie Wang(a)
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  2. **g**g Zhang
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  3. Mengjie **ao
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  4. Shudong Wang
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  5. Jie Wang(b)
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  6. Yuanfang Guo
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  7. Yufeng Tang
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  8. Junlian Gu
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Corresponding author

Correspondence to Junlian Gu.

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Wang(a), J., Zhang, J., **ao, M. et al. Molecular mechanisms of doxorubicin-induced cardiotoxicity: novel roles of sirtuin 1-mediated signaling pathways. Cell. Mol. Life Sci. 78, 3105–3125 (2021). https://doi.org/10.1007/s00018-020-03729-y

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  • DOI: https://doi.org/10.1007/s00018-020-03729-y

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