Resveratrol prevents apoptosis in K562 cells by inhibiting lipoxygenase and cyclooxygenase activity

Eur J Biochem. 1999 Oct 1;265(1):27-34. doi: 10.1046/j.1432-1327.1999.00630.x.


The natural polyphenolic compound resveratrol (trans-3,4', 5-trihydroxystilbene) is shown to prevent apoptosis (programmed cell death) induced in human erythroleukemia K562 cells by hydrogen peroxide and other unrelated stimuli. Resveratrol reversed the elevation of leukotriene B4 (from 6.40 +/- 0.65 to 2.92 +/- 0.30 protein-1) and prostaglandin E2 (from 11.46 +/- 1.15 to 8.02 +/- 0.80 protein-1), induced by H2O2 challenge in K562 cells. The reduction of leukotriene B4 and prostaglandin E2 correlated with the inhibition of the 5-lipoxygenase activity, and the cyclooxygenase and peroxidase activity of prostaglandin H synthase, respectively. Resveratrol also blocked lipoperoxidation induced by hydrogen peroxide in K562 cell membranes. Resveratrol was found to act as a competitive inhibitor of purified 5-lipoxygenase and 15-lipoxygenase and prostaglandin H synthase, with inhibition constants of 4.5 +/- 0.5 microM (5-lipoxygenase), 40 +/- 5.0 microM (15-lipoxygenase), 35 +/- 4.0 microM (cyclooxygenase activity of prostaglandin H synthase) and 30 +/- 3.0 microM (peroxidase activity of prostaglandin H synthase). Altogether, the results reported here suggest that the anti-apoptotic activity of resveratrol depends on the direct inhibition of the main arachidonate-metabolizing enzymes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Arachidonate 15-Lipoxygenase / drug effects
  • Arachidonate 5-Lipoxygenase / drug effects
  • Cyclooxygenase Inhibitors / pharmacology
  • Humans
  • K562 Cells
  • Lipoxygenase / drug effects*
  • Lipoxygenase Inhibitors / pharmacology
  • Oxidative Stress
  • Prostaglandin-Endoperoxide Synthases / drug effects*
  • Resveratrol
  • Stilbenes / pharmacology*


  • Cyclooxygenase Inhibitors
  • Lipoxygenase Inhibitors
  • Stilbenes
  • Lipoxygenase
  • Arachidonate 15-Lipoxygenase
  • Arachidonate 5-Lipoxygenase
  • Prostaglandin-Endoperoxide Synthases
  • stilbene oxide
  • Resveratrol