UV-induced apoptosis in resistant HeLa cells.

Recently, apoptosis (genetically programmed cell death) induced by UV has been documented in some cell culture models. However, the significance of apoptosis in UV-induced cytotoxicity and resistance is uncertain. In this study, we investigated the induction of apoptosis in HeLa cells and its role in acquired UV-resistance. The membrane receptor Fas was induced to assembly, and its immediate downstream target, caspase-8, was induced by UV in a dose- and time-dependent manner. Caspase-10, another possible candidate for forming the death-inducing signaling complex with Fas, was also activated in a dose- and time-dependent manner. There was significant activation of caspase 9, 3 and 2 by UV. The apoptotic pathways appeared to be normal in acquired UV-resistant HeLa cells. In addition, there was a UV dose-dependent induction of chromatin condensation in both parental and UV-resistant cells. However, resistant cells displayed significant reduction in chromatin condensation at lower doses. Inhibition of caspase-3 activation by specific inhibitor significantly reduced the chromatin condensation in both cell types, and unexpectedly, the difference between the two cell lines was completely eradicated, suggesting that the caspase-3 pathway plays a significant role in reducing apoptosis in resistant cells. The results indicate that UV induces apoptosis by direct activation of apoptotic proteins in HeLa and resistant cells. Although resistant cells displayed partial inhibition of UV-induced apoptosis through the caspase-3 pathway, there was no consistent difference in the activation of this and related caspase-9 caspases compared to parental HeLa cells.