Antitumor activity of thymoquinone against fibrosarcoma tumorigenesis

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The potential antitumor effect of thymoquinone (TQ), the main constituent of the volatile oil of Nigella sativa seed, on fibrosarcoma induced by 20-methylcholanthrene (MC)in male Swiss albino mice was investigated in vivo and in vitro. Subcutaneous injection of MC produced 93% tumor incidence and the onset of tumor appeared within 8 weeks. Administration of TQ (0.01% in drinking water) one week before and thereafter MC treatment until the end of the experiment resulted in significant inhibition of MC-induced fibrosarcoma when compared with the group receiving MC alone. TQ significantly inhibited the tumor incidence and tumor burden by 43% and 34%, respectively. Moreover, TQ administration delayed the onset of MC-induced fibrosarcoma (tumors appeared at 12th weeks) and produced less MC-induced mortality. Lipid peroxide accumulation, decreased glutathione (GSH) content and decreased activities of glutathione S-transferase (GST) and quinone reductase (QR) were observed in the liver of MC-induced tumor-bearing mice. TQ alone showed a significant induction in the enzyme activities of hepatic GST and QR. Mice treated with TQ along with MC showed reduction in hepatic lipid peroxides and increased GSH content, and increased enzyme activities of GST and QR compared to the control group. The in vitro studies showed that TQ inhibited the survival of fibrosarcoma cells with IC50 of 15 μM. On the other hand, TQ inhibited the incorporation of [3H]thymidine in fibrosarcoma cells with IC50 of 1μM. The present data indicate the potential of TQ as a powerful chemopreventive agent against MC-induced fibrosarcoma tumors. The possible modes of action of TQ may be through its antioxidant activity and interference with the DNA synthesis coupled with enhancement of detoxification processes.

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