Protein kinase C zeta isoform is critical for proliferation in human glioblastoma cell lines

Previous studies have confirmed that proliferation in glioblastoma cell lin es can be blocked by non-isoform specific protein kinase C (PKC) inhibitors , e.g calphostin C, staurosporine. However, the exact mechanism of PKC invo lvement is poorly understood. The aim of this study was to explore the role of specific PKC isoforms in the aberrant growth of glioblastoma. Identific ation of the isoform(s) critical for proliferation in glioblastoma would pr esent a better target for the design of chemotherapeutic strategies. To thi s end, we screened expression on PKC isoforms in four human glioblastoma ce ll lines both when proliferating and in a quiescent state using western ass ays. PKC isoforms alpha, beta I, beta II and zeta were found to be expresse d in all cell lines. PKC epsilon was detected in three out of four cell lin es and PKC eta was detected in one out of four cell lines. Quiescence of gr owth resulted in down-regulation of PKC epsilon. We examined the role of th ese isoforms by studying the effect of PKC isoform-specific inhibitors bisi ndolylmaleimide-I and Go6976 on proliferation in a panel of four human glio blastoma cell lines. Inhibition of PKC alpha and epsilon had no effect on p roliferation, suggesting that previous studies targeting PKC alpha may not be of therapeutic benefit. More significantly, it was shown that inhibition of PKC zeta blocked proliferation. This suggests that the inhibition of PK C zeta may be an important chemotherapeutic target for arresting growth in glioblastoma.