Enhancement of X-ray cell killing in cultured mammalian cells by the protein phosphatase inhibitor calyculin A.

Effects of calyculin A, a potent inhibitor of protein phosphatases 1 and 2A, on X-ray cell killing and chromatin structure were studied using cultured mammalian cells (BHK21). Calyculin A at concentrations of 2.5-20 nM enhanced X-ray cell killing when exponentially growing BHK21 cells were treated with calyculin A for 30 min after X-irradiation. A 30-min treatment with this drug induced chromatin condensation transiently. These results suggest that the enhancement of X-ray cell killing by calyculin A is caused by the events associated with chromatin condensation. Protein phosphatase-targeting drugs may represent a new class of radiation sensitizers.