STAUROSPORINE DIFFERENTIALLY INHIBITS GLIOMA VERSUS NONGLIOMA CELL-LINES

We have previously demonstrated that the protein kinase C (PKC) activity of human glioma cell lines was significantly elevated (by 3 orders of magnitude) when compared to non-malignant adult human glia, and that the proliferation rate of several established human glioma cell lines correlated with the measured protein kinase C activity. The purpose of this study was to determine whether 1) elevated PKC activity was also a characteristic of fast growing cell lines of non-glial origin, 2) the proliferation rate of non-glioma cell lines correlated with their PKC activity and 3) the proliferation of non-glioma cell lines could be inhibited by staurosporine, a relatively selective PKC inhibitor, which significantly attenuates the growth of glioma cells. Eight established human non-glioma cell lines (bladder, colorectal, rhabdomyosarcoma-oligodendrocyte hybrid, melanoma, cervix, and fibroblast) were compared to the highly proliferative A172 glioma cell line. PKC activity was significantly higher in the glioma cell lines even though 3 of 8 of the non-glioma lines had higher proliferation rates than A172. In non-glioma cell lines, no correlation was found between the PKC activity and proliferation rates. Staurosporine was more effective in decreasing the proliferation of three glioma cell lines compared to the non-glioma cell lines. We conclude that PKC activity is differentially increased in glioma cell lines and that their proliferation rate is more sensitive to inhibition by staurosporine. Targetting the PKC system may prove to be of therapeutic benefit to patients with malignant gliomas.