Protein kinase C inhibition by UCN-01 induces apoptosis in human glioma cells in a time-dependent fashion.

摘要: Recent studies in our laboratory have shown that UCN-01 (7-hydroxystaurosporine), which is a derivative of the non-selective protein kinase inhibitor staurosporine exhibits relative selectivity for C (PKC), potent glioma growth vitro and vivo models. This agent both cytotoxic cytostatic effects, depending on time period drug exposure. In present study, we examined whether UCN-01-induced cytotoxicity correlated with induction apoptosis, characterized further course this process as prelude to application clinical trials. We first demonstrated effects were associated morphological features apoptosis. Secondly, identified electrophoretic apoptosis semiquantitatively at series points using field inversion gel electrophoresis. These showed peak high-molecular-weight DNA fragmentation after 3-6 days treatment. Thirdly, measured percentage cells undergoing various terminal transferase-catalyzed situ end-labeling technique, confirmed time- concentration-dependent increase apoptotic cell numbers. progressive decrease viable assessed by trypan blue exclusion. Cell killing peaked within 2-4 beginning treatment, but continued lower level ensuing days. Taken together, these extended periods exposure are needed optimal manifestation against cells, factor must be taken into consideration design future trials malignant gliomas.