Lipid peroxidation-mediated telomere shortening in hydroxyl radical-induced apoptosis in HeLa cells

Many anti-cancer drugs have been found to trigger apoptosis in tumor cells through the production of reactive oxygen species (ROS) including hydroxyl radicals (OH) regardless of chemical types. At the same time, telomerase is found to be associated with malignancy and reduced apoptosis. However, little is known about the linkage between ROS (such as OH) and telomerase/telomere. The focus of this investigation was to examine the possibie pathway of the apoptosis induced by OH production via Fe
²⁺
and H
2
O
2
. Results of the present study demonstrated that after exposure of HeLa cells to Fe
²⁺
-H
2
system, an increase in lipid peroxidation and reduction of GSH was observed. These events proceeded and triggered apoptosis, resulting in DNA fragmentation. More interestingly, we did not observe any changes of telomerase activity. However, the telomere length in apoptotic cells shortened significantly. We also found that GSH rescued OH-induced HeLa cell death and prevened telomere shortening, and that 3,3'-diethyoxadicarbocyanine (DODCB), a telomerase inhibitor, increased susceptibility of HeLa cells to OH-induced apoptosis. Our results suggest that OH-inruced telomere shortening is not through telomerase inhibition but possibiy a direct effect of OH on telomeres themselves via lipid peroxidation.