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Inhibitory effects of thymoquinone against 20-methylcholanthrene-induced fibrosarcoma tumorigenesis
1Department of Pharmacology and Toxicology, College of Pharmacy, Al-Azhar University, Nasr City, Cairo, Egypt.
Abstract:
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. Administration of TQ (0.01% in drinking water) I week before and after MC treatment significantly inhibited the tumor incidence and tumor burden by 43% and 34%, respectively, compared with the results in the group receiving MC alone. Moreover, TQ delayed the onset of MC-induced fibrosarcoma tumors that appeared at 12 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 as compared to results of the control group. The in vitro studies showed that TQ inhibited the survival of fibrosarcoma cells with IC50 of 15 microM. Conversely, TQ inhibited the incorporation of [3H] thymidine in fibrosarcoma cells with IC50 of microM. Our 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.
Insights
Thymoquinone (TQ) shows potential as a chemopreventive agent against fibrosarcoma. It inhibited tumor growth and survival in mice and cancer cells, possibly via antioxidant and DNA synthesis interference.
Area of Science:
- Pharmacology
- Oncology
- Biochemistry
Background:
- 20-methylcholanthrene (MC) induces fibrosarcoma in mice.
- Thymoquinone (TQ) is a key compound in Nigella sativa seeds.
- Investigating TQ's chemopreventive potential against MC-induced fibrosarcoma.
Purpose of the Study:
- To evaluate the antitumor effects of TQ against MC-induced fibrosarcoma.
- To explore the underlying mechanisms of TQ's action.
- To assess TQ's impact on tumor incidence, burden, mortality, and specific biochemical markers.
Main Methods:
- In vivo studies: TQ administration before and after MC treatment in mice.
- In vitro studies: TQ treatment of fibrosarcoma cells.
- Biochemical analysis: Measurement of lipid peroxides, glutathione (GSH), glutathione S-transferase (GST), and quinone reductase (QR) in liver tissues.
Main Results:
- TQ significantly inhibited tumor incidence (43%) and burden (34%) in MC-treated mice.
- TQ delayed tumor onset and reduced mortality, while restoring antioxidant markers (GSH, GST, QR) and reducing lipid peroxides.
- In vitro, TQ inhibited fibrosarcoma cell survival (IC50 = 15 microM) and DNA synthesis.
Conclusions:
- Thymoquinone demonstrates significant chemopreventive effects against MC-induced fibrosarcoma.
- TQ's mechanisms involve antioxidant activity, interference with DNA synthesis, and enhanced detoxification.
- TQ holds promise as a chemopreventive agent for fibrosarcoma.