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. Epub 2020 May 26.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cardiotonic Agents / pharmacology*
  • Cardiotoxicity / drug therapy
  • Cardiotoxicity / genetics
  • Computational Biology
  • Databases, Genetic
  • Disease Models, Animal
  • Doxorubicin
  • Gene Expression Profiling
  • Heart / drug effects
  • Heart Diseases / chemically induced
  • Heart Diseases / drug therapy*
  • Heart Diseases / genetics
  • Metabolic Networks and Pathways / genetics*
  • Myocytes, Cardiac / drug effects
  • Phenanthrenes / pharmacology*
  • Rats
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects
  • Transcriptome / genetics*

Substances

  • Cardiotonic Agents
  • Phenanthrenes
  • Reactive Oxygen Species
  • cryptotanshinone
  • Doxorubicin