Involvement of intracellular cAMP in epirubicin-induced vascular endothelial cell injury

J Pharmacol Sci. 2016 Jan;130(1):33-7. doi: 10.1016/j.jphs.2015.12.010. Epub 2016 Jan 6.

Abstract

We investigated the involvement of intracellular cAMP in endothelial cell injury induced by epirubicin. Epirubicin-induced decrease in cell viability and increase in caspase-3/7 activity were reversed by a cAMP analog dibutyryl cAMP (DBcAMP) or an activator of adenylate cyclase forskolin concomitant with a phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine. Moreover, epirubicin-induced elevation of lipid peroxide levels was attenuated by DBcAMP. Interestingly, the exposure of epirubicin decreased intracellular cAMP levels before the onset of epirubicin-induced production of lipid peroxidation. These results suggest that intracellular cAMP plays an important role in epirubicin-induced endothelial cell injury.

Keywords: Endothelial cell; Epirubicin; cAMP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-3-isobutylxanthine / pharmacology
  • Albuterol, Ipratropium Drug Combination
  • Animals
  • Apoptosis / drug effects*
  • Bucladesine / pharmacology
  • Caspase 3 / metabolism
  • Caspase 7 / metabolism
  • Cell Survival / drug effects
  • Cells, Cultured
  • Colforsin / pharmacology
  • Cyclic AMP / metabolism
  • Cyclic AMP / physiology*
  • Endothelial Cells / drug effects*
  • Endothelial Cells / metabolism
  • Endothelial Cells / pathology*
  • Epirubicin / adverse effects*
  • Epirubicin / antagonists & inhibitors*
  • Lipid Peroxidation / drug effects
  • Lipid Peroxides / metabolism
  • Swine

Substances

  • Albuterol, Ipratropium Drug Combination
  • Lipid Peroxides
  • Colforsin
  • Epirubicin
  • Bucladesine
  • Cyclic AMP
  • Caspase 3
  • Caspase 7
  • 1-Methyl-3-isobutylxanthine