Background: Glioblastoma responds poorly to standard chemotherapy agents. The expression of a mutant, constitutively-active EGF receptor (EGFRvIII) is common in glioblastoma and contributes to chemotherapy resistance. We have assessed the cytotoxicity of an inhibitor of atypical protein kinase C on glioblastoma cells expressing EGFRvIII.
Materials and methods: Glioblastoma cells were treated with a peptide-based atypical protein kinase C inhibitor. Apoptosis was assessed by morphological criteria, TUNEL assays, annexin V staining, Hoechst staining and colorimetric assays for cell viability.
Results: The atypical protein kinase C inhibitor induced rapid apoptosis in glioblastoma cells expressing EGFRvIII and killed these cells with an IC50 of 16 microM. Glioblastoma cells which do not express EGFRvIII were less sensitive. Apoptosis was not affected by caspase inhibitors and occurred without detectable caspase activation.
Conclusion: An atypical protein kinase C inhibitor induces rapid apoptosis in glioblastoma cells by a caspase-independent mechanism that is enhanced, rather than inhibited, by EGFRvIII.