Hesperidin alleviates oxidative stress and downregulates the expressions of proliferative and inflammatory markers in azoxymethane-induced experimental colon carcinogenesis in mice
Colon cancer is a common malignant neoplasm causing huge morbidity and mortality worldwide. Current therapeutic interventions are unsatisfying, which necessitates novel chemopreventive strategies. The present study was intended to elucidate the chemopreventive efficacy of hesperidin against azoxymethane (AOM)-induced mouse colon carcinogenesis.
Materials and methods
Swiss albino mice were subjected to intraperitoneal injections of AOM once a week for 3 consecutive weeks. Hesperidin treatments were provided in the initiation or post-initiation phases. The number and multiplicity of aberrant crypt foci (ACF), tumor incidence and antioxidant status were determined. Histopathological analyses, proliferating cell nuclear antigen (PCNA) index and modulations in the expression of inflammatory markers such as nuclear factor kappa B (NF-κB), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were studied.
Hesperidin treatments significantly inhibited the number and multiplicities of AOM-induced ACF and tumor incidence. Hesperidin reduced oxidative stress parameters and enhanced antioxidant status. A marked decrease in the PCNA index was evident on hesperidin administration. Hesperidin treatments caused a prominent downregulation of NF-κB and its target molecules iNOS and COX-2, thereby combating inflammation.
This study proves the chemopreventive efficacy of hesperidin against the deleterious traits of colon carcinogenesis including accelerated proliferation, inflammation and persistent oxidative stress.
KeywordsHesperidin Colon carcinogenesis PCNA NF-κB COX-2 iNOS
This work was supported by a fund from the Council of Scientific and Industrial Research (CSIR), New Delhi. We thank Dr. Ramamurthy, Director, Ultra-fast Process Laboratory, University of Madras for his help in confocal imaging.
- 7.Boateng J, Verghese M, Shackelford L, Walker LT, Khatiwada J, Ogutu S, Williams DS, Jones J, Guyton M, Asiamah D, Henderson F, Grant L, DeBruce M, Johnson A, Washington S, Chawan CB. Selected fruits reduce azoxymethane (AOM)-induced aberrant crypt foci (ACF) in Fisher 344 male rats. Food Chem Toxicol. 2007;45:725–32.PubMedCrossRefGoogle Scholar
- 19.Hall PA, Levison DA, Woods AL, Yu CCW, Kellock DB, Watkins JA, Barnes DM, Gillett CE, Camplejohn R, Dover R, Waseem NH, Lane DP. Proliferating cell nuclear antigen (PCNA) immunolocalization in paraffin sections: an index of cell proliferation with evidence of deregulated expression in some neoplasms. J Pathol. 1990;162:285–94.PubMedCrossRefGoogle Scholar
- 27.Cederbaum AI, Cohen G. In: Packer L, editor, Methods in enzymology. San Diego: Academic Press; 1984. pp. 516–522.Google Scholar
- 33.Omaye ST, Urnbull JB, Sauberlich HE. Selected methods for the determination of ascorbic acid in animal cells, tissues and fluids. Methods Enzymol. 1979;62:1–11.Google Scholar
- 39.Leonardi T, Vanamala J, Taddeo SS, Davidson LA, Murphy ME, Patil BS, Wang N, Carroll RJ, Chapkin RS, Lupton JR, Turner ND. Apigenin and naringenin suppress colon carcinogenesis through the aberrant crypt stage in azoxymethane-treated rats. Exp Biol Med. 2010;23:710–7.Google Scholar
- 46.Burton GW, Ingold KU. Auto oxidation of biological molecules: the antioxidant activity of vitamin E and related chain-breaking phenolic antioxidants in vitro. J Am Chem Soc. 1981;103:64–72.Google Scholar