Glioblastoma is a highly aggressive type of
brain cancer which currently has limited options for treatment. It is imperative to develop combination
therapies that could cause apoptosis in
glioblastoma. The aim of this study was to characterize the affect of modified ICA-1, a
PKC-iota inhibitor, on the growth pattern of various
glioblastoma cell lines. T98G and U87
glioblastoma cells were treated with ICA-1 alone and the absolute cell numbers of each group were determined for cell growth expansion analysis, cell viability analysis, and cell death analysis. Low dose ICA-1 treatment alone significantly inhibited cell growth expansion of high density
glioblastoma cells without inducing cell death. However, the high dose ICA-1 treatment regimen provided significant apoptosis for
glioblastoma cells. Furthermore, this study was conducted to use a two layer molecular level approach for treating
glioblastoma cells with ICA-1 plus an apoptosis agent,
tumor-necrosis factor-related apoptosis-inducing
ligand (TRAIL), to induce apoptosis in such chemo-refractory
cancer cells. Following ICA-1 plus TRAIL treatment, apoptosis was detected in
glioblastoma cells via the TUNEL assay and via flow cytometric analysis using
Annexin-V FITC/PI. This study offers the first evidence for ICA-1 alone to inhibit
glioblastoma cell proliferation as well as the novel combination of ICA-1 with TRAIL to cause robust apoptosis in a
caspase-3 mediated mechanism. Furthermore, ICA-1 plus TRAIL simultaneously modulates down-regulation of
PKC-iota and c-Jun.