2. Academic Validation
  3. Pretreatment of 3-MA prevents doxorubicin-induced cardiotoxicity through inhibition of autophagy initiation

Pretreatment of 3-MA prevents doxorubicin-induced cardiotoxicity through inhibition of autophagy initiation

  • Toxicology. 2023 Apr 14;153512. doi: 10.1016/j.tox.2023.153512.
Xiaofan Sun 1,  Heng Meng 2,  Jia Xiao 3,  Fangshu Liu 1,  Juan Du 4,  Hui Zeng 5
Affiliations

Affiliations

  • 1 Department of Hematology.
  • 2 Department of Neurology and Stroke Center.
  • 3 Clinical Medicine Research Institute and Department of Metabolic and Bariatric Surgery,The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, 510630, China.
  • 4 Department of Hematology. Electronic address: du.juan@u.nus.edu.
  • 5 Department of Hematology. Electronic address: androps2011@hotmail.com.
PMID: 37062353 DOI: 10.1016/j.tox.2023.153512
Abstract

Anthracycline antineoplastics are effective in the treatment of hematological malignancies and solid tumors. However, the anthracycline-induced cardiotoxicity (AIC) limits their use as chemotherapeutic agents. Autophagy-based therapies have been explored to prevent AIC. Yet, whether inhibition of Autophagy during its early stage could alleviate AIC remains unclear. In this study, we firstly observed the activation of Autophagy during AIC in both cardiomyocyte cell lines AC16 and H9c2. Moreover, knockdown of Atg7, a key regulatory factor in early Autophagy, could ameliorate the effects of DOX-induced AIC. Importantly, the use of early Autophagy Inhibitor 3-MA protected cardiomyocyte cells from DOX-induced cardiotoxicity in vitro and in a chronic AIC mouse model. Our findings demonstrate that inhibiting early stage of Autophagy may be an effective preventative therapeutic strategy to protect cardiac function from AIC.

Keywords

3-MA; Atg7; Autophagy; Cardiotoxicity; Doxorubicin.

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