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Chemopreventive potential of dietary bioflavonoids against 20-methylcholanthrene-induced tumorigenesis
V Elangovan1, N Sekar, S Govindasamy
1Department of Biochemistry, University of Madras, India.
Abstract:
The effect of dietary supplementation of flavonoidal compounds such as quercetin, rutin, luteolin and (+)-catechin on the incidence of fibrosarcoma induced by 20-methylcholanthrene (20-MC) in male Swiss albino mice was observed. Subcutaneous injection of 20-MC produced 100% tumor incidence and the onset of tumor appeared within 7 weeks, while flavonoid-treated mice (1% quercetin- and luteolin-mixed diets) produced tumors in the 9th week, and the tumor incidences in mice treated with quercetin- and luteolin-mixed diets were 52% and 60%, respectively. Subcutaneous administration of 20-MC along with the flavonoidal compounds (quercetin, luteolin) was found to have significant effect on tumor expression. The compounds rutin and (+)-catechin did not influence tumor expression in both experiments. Elevated levels of lipid peroxides, cytochrome P450 and decreased activity of glutathione-S-transferase (GST) were observed in the tumor bearing animals. Test-diet-treated animals showed reduction in the lipid peroxides and cytochrome P450, and increased activity of GST (P < 0.001). In vitro [3H]thymidine incorporation showed the inhibition of DNA synthesis in fibrosarcoma cells by the flavonoids. The possible mode of action of the flavonoidal compounds may be through their influence on the initiation and promotion phases of the carcinogenic process coupled with enhancement of the detoxification process.
Insights
Dietary flavonoids like quercetin and luteolin significantly reduced fibrosarcoma incidence in mice. These compounds inhibited DNA synthesis and enhanced detoxification, offering potential cancer prevention strategies.
Area of Science:
- Biochemistry
- Pharmacology
- Oncology
Background:
- Flavonoids are plant-derived polyphenolic compounds with known antioxidant and anti-inflammatory properties.
- Dietary supplementation is explored for cancer chemoprevention, but specific mechanisms require elucidation.
Purpose of the Study:
- To investigate the chemopreventive effects of dietary flavonoids (quercetin, rutin, luteolin, (+)-catechin) against 20-methylcholanthrene (20-MC)-induced fibrosarcoma in mice.
- To explore the impact of these flavonoids on tumor incidence, expression, and key biochemical markers associated with carcinogenesis.
Main Methods:
- Male Swiss albino mice were administered 20-methylcholanthrene (20-MC) to induce fibrosarcoma.
- Mice received dietary supplementation with quercetin, rutin, luteolin, or (+)-catechin.
- Tumor incidence, onset, and expression were monitored.
- Levels of lipid peroxides, cytochrome P450, and glutathione-S-transferase (GST) activity were assessed in tumor-bearing and treated animals.
- In vitro DNA synthesis inhibition was measured using [3H]thymidine incorporation.
Main Results:
- 20-MC induced 100% fibrosarcoma incidence within 7 weeks.
- Dietary quercetin (52% incidence) and luteolin (60% incidence) significantly reduced tumor incidence and delayed onset (9th week).
- Rutin and (+)-catechin did not affect tumor expression.
- Flavonoid treatment reduced lipid peroxides and cytochrome P450, while increasing GST activity (P < 0.001).
- In vitro studies demonstrated flavonoid inhibition of DNA synthesis in fibrosarcoma cells.
Conclusions:
- Quercetin and luteolin exhibit significant chemopreventive effects against 20-MC-induced fibrosarcoma.
- These flavonoids may act by inhibiting tumor initiation/promotion and enhancing detoxification pathways.
- Flavonoids show potential as dietary agents for cancer prevention through modulation of key carcinogenic processes.