Thymoquinone induces apoptosis in human glioblastoma cell lines

Nigella sativa L. seeds have been traditionally employed for thousands of years as a spice and food preservative, as well as a protective and curative remedy for the treatment of inflammations, liver disorders, and arthritis in Middle Eastern. The main constituent of volatile oil is the thymoquinone (TQ). TQ is the bioactive component that possesses antioxidant, anti-inflammatory, anti-neoplastic, and hepato-protective properties. Previous studies demonstrated anti-cancer properties of TQ in several in vitro and in vivo tumor models. However, therapeutic efficacy of TQ has not been evaluated in glioblastoma. We investigated the effects of TQ against two human glioblastoma cell lines, U87 MG (p53 wild type) and T98G (p53 mutant). TQ decreases cell survival in a dose and time-dependent manner, and more significantly in U87 MG cells than in T98G cells. The cells exposed to 25, 50, and 100 µM TQ for 24 h showed morphological and biochemical features of apoptosis. Morphological changes, nuclear condensation, DNA fragmentation, caspases-9 and -3 activities, and reactive oxygen species (ROS) production were determined. Cell death was found to be apoptotic involving intrinsic pathways as evidenced by increase of caspase-9 activity. ROS were elevated following TQ treatment and antioxidant N-acetyl-cysteine prevented cell death in both cell lines. These findings suggest that TQ induces apoptosis via a mechanism involving ROS and oxidative stress pathway.