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Published on: October 21, 2012
UV-induced apoptosis in resistant HeLa cells
1Department of Biochemistry, Chang Gung University, Taoyuan, Taiwan, Republic of China.
Abstract:
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.
Insights
UV radiation induces apoptosis (programmed cell death) in HeLa cells by activating caspases. Acquired UV-resistant cells partially inhibit this process via the caspase-3 pathway, reducing UV-induced cytotoxicity.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- UV radiation is a known inducer of cell death, but its role in cytotoxicity and resistance is not fully understood.
- Apoptosis, or programmed cell death, is a critical cellular process.
- Understanding UV-induced apoptosis is key to understanding cellular resistance mechanisms.
Purpose of the Study:
- To investigate the induction of apoptosis in HeLa cells following UV exposure.
- To determine the role of apoptosis in acquired UV-resistance.
- To elucidate the specific caspase pathways involved in UV-induced cell death and resistance.
Main Methods:
- UV irradiation of HeLa and UV-resistant HeLa cells.
- Analysis of membrane receptor Fas assembly and activation of downstream caspases (caspase-8, -10, -9, -3, -2).
- Assessment of chromatin condensation as a marker of apoptosis.
- Inhibition of caspase-3 activation to evaluate its role in UV resistance.
Main Results:
- UV exposure dose- and time-dependently activated Fas, caspase-8, caspase-10, and other caspases (9, 3, 2) in HeLa cells.
- UV-resistant cells showed reduced chromatin condensation at lower UV doses compared to parental cells.
- Inhibition of caspase-3 significantly reduced chromatin condensation in both cell types, eliminating the difference between resistant and parental cells.
- No consistent difference in caspase-9 activation was observed between parental and resistant cells.
Conclusions:
- UV directly activates apoptotic proteins, including caspases, in both HeLa and UV-resistant cells.
- The caspase-3 pathway plays a significant role in reducing UV-induced apoptosis in acquired resistant cells.
- While resistant cells exhibit partial inhibition of UV-induced apoptosis via caspase-3, upstream caspase activation (caspase-9) shows no consistent difference compared to parental cells.

