Continued exposure of anti-cancer drugs to human iPS cell-derived cardiomyocytes can unmask their cardiotoxic effects

J Pharmacol Sci. 2019 Aug;140(4):345-349. doi: 10.1016/j.jphs.2019.08.005. Epub 2019 Aug 27.

Abstract

Although the cardiotoxicity of anti-cancer drugs is an important issue, the underlying mechanisms remain unknown. To develop a sensitive assay system for cardiotoxicity, we examined effects of anti-cancer drugs on contractile functions of human iPS cell-derived cardiomyocytes by using non-invasive motion field imaging analysis with extended drug exposure time. We succeeded in continuously measuring stable contractile function. The continued exposure revealed that the difference in cardiotoxicity between cardiotoxic doxorubicin and less toxic erlotinib was more evident after 8 days of treatment than with 3 days of treatment, suggesting that continued exposure improved the predictive power for cardiotoxicity of anti-cancer drugs.

Keywords: Cardio-oncology; anti-cancer drug; iPS cell.

MeSH terms

  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / pharmacology*
  • Cardiotoxicity / etiology*
  • Cells, Cultured
  • Doxorubicin / adverse effects
  • Doxorubicin / pharmacology
  • Erlotinib Hydrochloride / adverse effects
  • Erlotinib Hydrochloride / pharmacology
  • Humans
  • Induced Pluripotent Stem Cells / drug effects*
  • Myocardial Contraction / drug effects
  • Myocytes, Cardiac / drug effects*

Substances

  • Antineoplastic Agents
  • Doxorubicin
  • Erlotinib Hydrochloride