Hydroxyl radical-induced apoptosis in human tumor cells is associated withtelomere shortening but not telomerase inhibition and caspase activation

Reactive oxygen species (ROS) have been found to trigger apoptosis in tumor cells. At the same time, telomerase is found to be associated with maligna ncy and reduced apoptosis, However little is known about the linkage betwee n ROS such as (OH)-O-. and telomerase/telomere, To address the interrelatio ns between (OH)-O-. and telomerase/telomere in tumor cell killing, HeLa, 29 3 and MW451 cells were induced to undergo apoptosis with (OH)-O-. radicals generated via Fe2+-mediated Fenton reactions (0.1 mM FeSO4 plus 0.3-0.9 mM H2O2) and telomerase activity, telomere length were measured during apoptos is, We found that during (OH)-O-.-induced apoptosis, telomere shortening to ok place while no changes in telomerase activity were observed. Our results suggest that (OH)-O-.-induced telomere shortening is not through telomeras e inhibition but possibly a direct effect of (OH)-O-. on telomeres themselv es indicating that telomere shortening but not telomerase inhibition is the primary event during (OH)-O-.-induced apoptosis, Strikingly, we also found that (OH)-O-.-induced apoptosis in HeLa cells is caspase-3-independent but is associated with reduction of mitochondrial transmembrane potential. Our results indicate that (OH)-O-. triggers apoptotic tumor cell death through a telomere-related, caspase-independent pathway. (C) 2001 Federation of Eu ropean Biochemical Societies. Published by Elsevier Science B.V, All rights reserved.