The membrane targeted apoptosis modulators erucylphosphocholine and erucylphosphohomocholine increase the radiation response of human glioblastoma cell lines in vitro

While all cell lines showed high intrinsic resistance against radiation-induced apoptosis as determined by fluorescence microscopy, treatment with ErPC and ErPC3 strongly increased sensitivity of the cells to radiation-induced cell death (apoptosis and necrosis). T98G cells were most responsive to the combined treatment revealing highly synergistic effects while A172 showed mostly additive to synergistic effects, and U87MG cells sub-additive, additive or synergistic effects, depending on the respective radiation-dose, drug-concentration and treatment time. Combined treatment enhanced therapy-induced damage of the mitochondria and caspase-activation. Importantly, combined treatment also increased radiation-induced eradication of clonogenic T98G cells as determined by standard colony formation assays.Our observations make the combined treatment with ionizing radiation and the membrane targeted apoptosis modulators ErPC and ErPC3 a promising approach for the treatment of patients suffering from malignant glioma. The use of this innovative treatment concept in an in vivo xenograft setting is under current investigation.During the last decades there has been only little progress in the therapy of malignant glioma including the most aggressive manifestation glioblastoma multiforme (GBM). This infiltrative and destructive growing tumor is still almost uniformly fatal with a life expectancy of a few weeks to several months. Standard therapy consisting of surgery with postoperative external-beam radiation therapy (RT) prolongs median survival times to 9–12 months with almost no benefit of refined surgery, aggressive chemotherapy or improved technology of radiation therapy [1-4]. In this regard, low intrinsic sensitivity of the malignant cells to ionizing radiation and standard DNA-damaging drugs constitutes one of the critical parameters for treatment failure. Thus, novel treatment approaches are badly needed to improve prognosis of GBM patients. Since defective apoptosis ca