Glycyrrhizic acid suppresses 1,2‐dimethylhydrazine‐induced colon tumorigenesis in Wistar rats: Alleviation of inflammatory, proliferation, angiogenic, and apoptotic markers

Objectives Colon cancer is the major health disease related with high mortality. Glycyrrhizic acid (GA) is an active constituent of licorice with anti‐inflammatory and anticarcinogenesis effects. We investigated the chemopreventive potential of GA against 1,2‐dimethylhydrazine (DMH)‐induced colon tu...

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Veröffentlicht in:Environmental toxicology 2018-12, Vol.33 (12), p.1272-1283
Hauptverfasser: Khan, Rehan, Rehman, Muneeb U., Khan, Abdul Quaiyoom, Tahir, Mir, Sultana, Sarwat
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Sprache:eng
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Zusammenfassung:Objectives Colon cancer is the major health disease related with high mortality. Glycyrrhizic acid (GA) is an active constituent of licorice with anti‐inflammatory and anticarcinogenesis effects. We investigated the chemopreventive potential of GA against 1,2‐dimethylhydrazine (DMH)‐induced colon tumorigenesis in Wistar rats. Methods Glycyrrhizic acid was administered orally at the dose of 15 mg/kg b.wt. and DMH was administered at the dose of 20 mg/kg b.wt. once a week for first 15 weeks. All the rats were euthanized after 30 weeks. GA supplementation significantly inhibited the tumor incidence and multiplicity. Results Glycyrrhizic acid treatment reduced the expression of Ki‐67, proliferating cell nuclear antigen (PCNA), nuclear factor‐kappa B (NF‐kB), cyclooxygenase‐2 (COX‐2), induced nitric oxide synthase (iNOS), and vascular endothelial growth factor (VEGF) while enhanced the expression of p53, connexin‐43, b‐cell lymphoma‐2 (Bcl‐2), survivin, and cleaved caspase‐3. Glycyrrhizic acid also significantly ameliorated DMH‐induced decreased activities of caspase‐9 and caspase‐3. Furthermore, GA treatment reduced mast cells infiltration, attenuated the shifting of sialomucin to sulphomucin as well the levels of pro‐inflammatory cytokines. Conclusion The findings of the study suggest that GA has chemopreventive potential against DMH‐induced colon tumorigenesis plausibly through the attenuation of hyperproliferative responses, pro‐inflammatory cytokines level, inflammatory and angiogenic markers, and apoptotic responses.
ISSN:1520-4081
1522-7278
DOI:10.1002/tox.22635