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 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 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.
MacCarrone
M
M
Department of Experimental Medicine and Biochemical Sciences, University of Rome Tor Vergata, Italy.
Lorenzon
T
T
Guerrieri
P
P
Agrò
A F
AF
D017209:Apoptosis / Q000187:drug effects*; D001093:Arachidonate 15-Lipoxygenase / Q000187:drug effects; D001094:Arachidonate 5-Lipoxygenase / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D006801:Humans; D020014:K562 Cells; D008084:Lipoxygenase / Q000187:drug effects*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D018384:Oxidative Stress; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects*; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*
D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D013267:Stilbenes; D008084:Lipoxygenase; D001093:Arachidonate 15-Lipoxygenase; D001094:Arachidonate 5-Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; C025906:stilbene oxide; D000077185:Resveratrol