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Glycyrrhizic acid suppresses 1,2‐dimethylhydrazine‐induced colon tumorigenesis in Wistar rats: Alleviation of inflammatory, proliferation, angiogenic, and apoptotic markers
Author(s) -
Khan Rehan,
Rehman Muneeb U.,
Khan Abdul Quaiyoom,
Tahir Mir,
Sultana Sarwat
Publication year - 2018
Publication title -
environmental toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.813
H-Index - 77
eISSN - 1522-7278
pISSN - 1520-4081
DOI - 10.1002/tox.22635
Subject(s) - survivin , apoptosis , carcinogenesis , azoxymethane , proliferating cell nuclear antigen , chemistry , vascular endothelial growth factor , aberrant crypt foci , colorectal cancer , pharmacology , dimethylhydrazine , 1,2 dimethylhydrazine , nitric oxide synthase , cell growth , cancer research , nitric oxide , endocrinology , medicine , biochemistry , cancer , colonic disease , vegf receptors
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.