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

Authors


A. Finazzi Agrò, Department of Experimental Medicine and Biochemical Sciences, University of Rome ‘Tor Vergata’, Via di Tor Vergata 135, I-00133 Rome, Italy. Fax: + 39 067 259 6468, Tel.: + 39 067 259 6468, E-mail: finazzi@uniroma2.it

Abstract

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 pmol·mg protein−1) and prostaglandin E2 (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 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 µm (5-lipoxygenase), 40 ± 5.0 µm (15-lipoxygenase), 35 ± 4.0 µm (cyclooxygenase activity of prostaglandin H synthase) and 30 ± 3.0 µm (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.

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