2. Academic Validation
  3. Attenuation of doxorubicin-induced cardiotoxicity by cryptotanshinone detected through association analysis of transcriptomic profiling and KEGG pathway

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

  • Aging (Albany NY). 2020 May 26;12(10):9585-9603. doi: 10.18632/aging.103228.
Le Li 1,  Bin Wu 2 3,  Qiangqiang Zhao 3 4,  Jian Li 3,  Yunfeng Han 5,  Xiaohang Fan 6,  Junli Dong 7,  Pengcheng Li 2
Affiliations

Affiliations

  • 1 Department of Cardiology, The Third Xiangya Hospital, Central South University, Changsha, China.
  • 2 Laboratory 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.
  • 3 Department of Blood Transfusion, The Third Xiangya Hospital, Central South University, Changsha, China.
  • 4 Department of Hematology, Qinghai Provincial People's Hospital, Xi'ning, China.
  • 5 Department of Nuclear Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 6 Department of Pathophysiology, Scholl of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 7 Laboratory 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.
PMID: 32457254 DOI: 10.18632/aging.103228
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.

Keywords

cardiotoxicity; cryptotanshinone; doxorubicin; reactive oxygen species; transcriptomic profiling.

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