Abstract
Glioblastoma (GBM) is the most aggressive and common type of brain tumor in humans. Surgical resection followed by radiation and chemotherapy is the current standard treatment; however, due to the upregulation of several survival pathways, tumor recurrence is quite common with a median survival of 12 to 15 months. Therefore, there is an urgent need for more effective therapeutic strategies for the treatment of glioblastoma. Naturally occurring phytochemicals have steadily received much scientific attention, owing to the fact that many of these compounds have potent action against tumors. Thymoquinone (TQ) is the bioactive compound of the volatile oil extracted from the black seed, Nigella sativa. TQ has shown anti-oxidant, anti-inflammatory and anti-neoplastic actions with a selective cytotoxicity for human cancer cells compared to several normal cells. Here, we show that TQ is able to dose-dependently inhibit colony formation in three distinct glioblastoma cell lines (T98, U87 and Gli36), with the highly tumorigenic Gli36 being the most sensitive to the anti-proliferative effects of TQ. We also show that TQ induces persistent γ-H2AX activation, a marker of DNA double strand breaks, in a time- and dose-dependent manner. TQ also causes G2/M cell cycle arrest in GBM cells to a degree that correlates with the cells’ relative clonogenic sensitivity. Moreover, co-treatment with TQ and N-acetyl cysteine, a simple thiol nucleophile and antioxidant, prevented cell death, DNA double strand breaks, and cell cycle arrest. Taken together, our findings demonstrate that TQ is a potent inhibitor of GBM cell proliferation and growth, and that this effect may be mediated by generation of reactive oxygen species.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1983. doi:1538-7445.AM2012-1983
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