Par-4 Therapy Sensitizes Glioblastoma Cells to Radiotherapy and Chemotherapy

Glioblastoma multiforme (GBM) is the most aggressive and common neurological tumor and presents with a dismal prognosis. Currently treatments to treat GBM include surgery, radiation therapy, and chemotherapy, typically Temozolamide (TMZ). Recurrence, however, is almost inevitable and the median survival for these patients is only 14.6 months. This study explored the potential of sensitizing GBM cells with Prostate apoptosis response protein-4 (Par-4). Par-4 protein expression was up-regulated in three GBM cell lines in vitro followed by treatment with standard radiotherapy and chemotherapy regimens. Par-4 up-regulation in these cell lines increased apoptosis of tumor cells alone and in combination with chemotherapy, radiotherapy, or both. In addition, cells were treated with the phenylalkyl isoselenocyanate, ISC-4, to induce activation of Par-4, and the combined treatment of ISC-4 with Par-4 enhanced apoptosis in the GBM cells. Utilizing a molecular target for GBM could lead to more permanent regression of tumor in addition to increased response to therapies.