Reducing the radiation-induced G(2) delay causes HeLa cells to undergo apoptosis instead of mitotic death

Cells exposed to radiation may undergo death through apoptosis or mitotic death. HeLa cells predominantly undergo mitotic death after irradiation. Treatment of these cells with caffeine has been shown to shorten the G(2) delay after irradiation, and to decrease their survival. The kinase inhibitor staurosporine also decreases the radiation-induced G(2) delay in HeLa cells. Here we extend these findings to show that the decrease in radiation-induced G(2) delay mediated by caffeine or staurosporine is accompanied by a shift in the pathway of cell death from mitotic death to apoptotic death. The increase in apoptosis is further accompanied by decreased clonogenic survival after irradiation. Based on these findings we propose the hypothesis that one mechanism of enhancing cell killing by radiation is to trigger apoptosis by decreasing the G(2) delay induced by irradiation.