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Research Paper|Volume 12, Issue 10|pp 9585—9603

Attenuation of doxorubicin-induced cardiotoxicity by cryptotanshinone detected through association analysis of transcriptomic profiling and KEGG pathway

Le Li1, Bin Wu2,3, Qiangqiang Zhao3,4, Jian Li3, Yunfeng Han5, Xiaohang Fan6, Junli Dong7, Pengcheng Li2
  • 1Department of Cardiology, The Third Xiangya Hospital, Central South University, Changsha, China
  • 2Laboratory of Platelet and Endothelium Biology, Department of Transfusion Medicine, Wuhan Hospital of Traditional Chinese and Western Medicine (Wuhan No.1 Hospital), Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
  • 3Department of Blood Transfusion, The Third Xiangya Hospital, Central South University, Changsha, China
  • 4Department of Hematology, Qinghai Provincial People’s Hospital, Xi’ning, China
  • 5Department of Nuclear Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
  • 6Department of Pathophysiology, Scholl of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
  • 7Laboratory of Clinical Pharmacogenetics, Department of Pharmacy, Wuhan Hospital of Traditional Chinese and Western Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Received: August 19, 2019Accepted: April 16, 2020Published: May 26, 2020
https://doi.org/10.18632/aging.103228

Copyright © 2020 Li et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Objective: The cardiotoxicity of doxorubicin (DOX) reduces the quality of life and prognosis of cancer patients, and therefore its clinical application has been largely restricted. This study aimed to assess the effects of cryptotanshione (CPT) on DOX-induced rat cardiac insufficiency.

Results: CPT treatment significantly suppressed apoptosis in vitro. The oral administration of CPT significantly improved cardiac function in the rat model, reduced collagen production and suppressed apoptosis and the production of reactive oxygen species in the heart tissue. Transcriptomic profiling and its relevant bioinformatics analysis showed that CPT suppressed doxorubicin-induced cardiotoxicity by inhibiting p53 signaling pathway.

Conclusion: Transcriptomic profiling and bioinformatics analysis can be used to evaluate the cardio-protective effect of CPT through inactivating p53 signaling pathway in the doxorubicin-mediated myocardial damage model.

Methods: F-actin staining and flow cytometry were used to assess the effects of CPT on cardiomyocytes. In vivo, echocardiography and hemodynamic evaluation were used to assess the effects of CPT on the cardiac dysfunction in rats. Furthermore, transcriptomic profiling and bioinformatics analysis, as well as western blot analysis, were used to determine that CPT induced changes in the signaling pathways in the model.