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

ABSTRACT

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.