Enhancement of apoptosis in irradiated glioblastoma cells by pentoxifylline

The p53 gene is frequently mutated in human glioblastomas, which are highly resistant to radiation and chemotherapy. Pentoxifylline has recently been shown to sensitize breast cancer cells in which the wild-type p53 function was abrogated to cisplatin-induced apoptosis. In this study, the effect of pentoxifylline on three irradiated human glioblastoma cell lines, U87MG, which has the wild-type p53; U251, which has a mutant p53; and LN- Z308, which has no p53, was examined. After radiation, even at a dose as high as 20 Gy, typical apoptotic cells were rarely produced. G₂ cell cycle arrest was observed with all three cell lines. Significant G₁ cell population was only observed with U87MG cells, in which increased levels of p21/WAF1/Cip1 occurred. Pentoxifylline increased the amount of radiation-induced DNA fragmentation and apoptosis in p53-defective U251 and LN-Z308 cells. Colony formation assay demonstrated that pentoxifylline moderately enhanced the cell killing effect of irradiation in these cells.