Abstract 2952: The PKC-iota inhibitor ICA-1 combined with TRAIL for glioblastoma therapy.

Abstract

Abstract Glioblastoma multiforme is a very aggressive brain tumor. Temozolimide is the standard clinical therapy following surgery which offers a limited survival advantage. The low survival rates of glioblastoma patients require further investigation into pre-clinical combination therapy options with apoptosis abilities. One such chemotherapeutic approach is the use of the novel PKC-iota inhibitor, ICA-1, combined with rhTRAIL. T98G or U87 glioblastoma cells were treated with ICA-1 for 48h or 72h, respectively, with or without rhTRAIL in a 24-well format. Based on flow cytometric analysis, the overall apoptosis rate for the T98G cells exposed to ICA-1 plus TRAIL was the most significant with no distinction between early and late apoptosis rates. In addition, the immunofluorescence analysis showed higher T98G cell death for the combination therapy. Further flow cytometric analysis showed that ICA-1 plus TRAIL generated significantly more late apoptosis for U87 cells than any other treatment. The mechanism of action for this combinatorial therapy is currently under investigation. However, our in vitro data demonstrated that ICA-1 plus TRAIL induced 60-70% apoptosis in U87 glioblastoma cells and T98G glioblastoma cells which may offer a better survival advantage in pre-clinical animal models. Citation Format: Andrea N. McCray, Shraddha Desai, Mildred Acevedo-Duncan. The PKC-iota inhibitor ICA-1 combined with TRAIL for glioblastoma therapy. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2952. doi:10.1158/1538-7445.AM2013-2952