Glioblastoma is the most aggressive and common type of brain tumors in humans. Surgical resection followed by radiation and chemotherapy is the current standard treatment; however, due to up-regulation of several survival pathways, tumor recurrence is quite common with a median survival of 12 to 15 months. Therefore, there is an urge for more effective therapeutic strategies for the treatment of glioblastoma. Over years the use of natural compounds as anticancer agents acquired great importance. Thymoquinone (TQ) is the bioactive component of the volatile oil extracted from the black seed, Nigella sativa. TQ has shown anti-oxidant, anti-inflammatory, and anti-neoplastic actions in in-vitro and in-vivo models with a selective cytotoxicity for human cancer cells compared to several normal cells. Here, we report that TQ greatly inhibited cell proliferation of radioresistant glioma cells (U87 and T98) in a concentration-dependent manner. Moreover, TQ mediated reactive oxygen species-induced DNA breaks in glioma cells, as detected by the appearance of post-DNA damage sensitive marker γH2AX. Our results also showed that TQ up-regulated p53 in U87 cells while down-regulated phospho-Akt in T98 cells in a dose-dependent manner. Current investigations are ongoing to use TQ in combination with ionizing radiation as a promising modality to overcome resistance, thereby reducing ionizing radiation doses used for glioma treatment. This work was supported by NIH grants CA93413, ES2388 and ES12991 to A. A. W.
|Publisher||American Association for Cancer Research|