Open AccessResveratrol prevents apoptosis in K562 cells by inhibiting lipoxygenase and cyclooxygenase activity
Author(s) -
Maccarrone Mauro,
Lorenzon Tatiana,
Guerrieri Pietro,
Agrò Alessandro Finazzi
Publication year - 1999
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1046/j.1432-1327.1999.00630.x
Subject(s) - resveratrol , cyclooxygenase , chemistry , prostaglandin , arachidonate 5 lipoxygenase , lipoxygenase , prostaglandin e , biochemistry , peroxidase , prostaglandin e2 , apoptosis , enzyme , arachidonic acid , biology , endocrinology
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 H 2 O 2 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 µ m (5‐lipoxygenase), 40 ± 5.0 µ m (15‐lipoxygenase), 35 ± 4.0 µ m (cyclooxygenase activity of prostaglandin H synthase) and 30 ± 3.0 µ 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.