SENSITIZATION OF C6 GLIOMA-CELLS TO RADIATION BY STAUROSPORINE, A POTENT PROTEIN-KINASE-C INHIBITOR

The effect of staurosporine, a potent protein kinase C (PKC) inhibitor, on the sensitivity to radiation has been investigated in C6 glioma cells. Pretreatment of C6 cells with staurosporine at the concentrations over 1 nM resulted in an enhancement of sensitivity to irradiation. At a concentration of 5 nM, staurosporine caused significant radiosensitization of the cells, either it was administered 1) before and during irradiation. or 2) continuously before, during, and after irradiation, with a reduced D0 (the 37% survival dose) from 3.8 Gy to 2.9 Gy and 3.0 Gy, respectively, (p < 0.03). Since the viability of C6 cells was not affected by staurosporine alone at the concentrations tested, the radiosensitizing effect of staurosporine was considered to be mediated via suppression of PKC. Furthermore, another potent PKC inhibitor H-7, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride, also sensitized C6 cells to irradiation, while HA1004, N-(2-guanidinoethyl)-5-isoquinolinesulfonamide hydrochloride a potent inhibitor for cAMP-dependent protein kinase, failed to affect the radiosensitivity in this cells. Therefore, staurosporine-induced sensitization of C6 cells to radiation may at least in part be mediated by its inhibitory activity for PKC. Staurosporine represents a new agent for radiosensitization and may prove usefulness in studying the mechanisms responsible for radio-resistance and -sensitivity in glioma cells.