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

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 B-4 (from 6.40 +/- 0.65 to 2.92 +/- 0.30 pmol.mg protein(-1)) and prostaglandin E-2 (from 11.46 +/- 1.15 to 8.02 +/- 0.80 nmol.mg protein(-1)), induced by H2O2 challenge in K562 cells. The reduction of leukotriene B-4 and prostaglandin E-2 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 mu M (5-lipoxygenase), 40 +/- 5.0 mu M (15-lipoxygenase), 35 +/- 4.0 mu M (cyclooxygenase activity of prostaglandin H synthase) and 30 +/- 3.0 mu M (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.