Indian Journal of Animal Research

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Research Article

Indian Journal of Animal Research, volume 51 issue 6 (december 2017) : 1120-1124

Halofuginone may suppresses azoxymethane-induced serum tumor necrosis factor-a synthesis and aberrant crypt foci progression in rat colon

Orhan Corum, Ozgur Ozdemir, Enver Yazar
1<p>Department of Pharmacology and Toxicology,&nbsp;Veterinary Faculty, University of Dicle, Diyarbakir-21280, Turkey.</p>
Cite article:- Corum Orhan, Ozdemir Ozgur, Yazar Enver (2017). Halofuginone may suppresses azoxymethane-induced serum tumor necrosis factor-a synthesis and aberrant crypt foci progression in rat colon . Indian Journal of Animal Research. 51(6): 1120-1124. doi: 10.18805/ijar.v0i0f.7600.

ABSTRACT

The aim of this research was to investigate the effect of halofuginone on the progression of azoxymethane-induced colon cancer in rats. A total of 38 male Wistar albino rats were divided into 4 groups: Control (n=8), Halofuginone (n=10, 0.4 mg/kg, PO, SID), Cancer (n=10, azoxymethane, 15 mg/kg, IP, once a week for two weeks) and Cancer + Halofuginone (n=10). After 18 weeks, blood samples were taken under anesthesia and all animals were sacrificed. Aberrant crypt foci in the colon were stained with methylene blue. Blood cytokines, thiobarbituric acid reactive substances, 13,14-dihydro-15-keto-prostaglandin F2a levels, hemogram and biochemical values were  measured. The tumor necrosis factor-a level in the Cancer group was higher (P<0.05) than in other groups, while higher numbers of aberrant crypt foci were found in the Cancer group compared with the Cancer + Halofuginone group (P<0.05). In summary, it may be stated that halofuginone may warrant evaluation as a supportive drug in the treatment of colon cancer in the future.

REFERENCES


  1. Abramovitch, R., Itzik, A., Harel, H., Nagler, A., Vlodavsky, I. and Siegal, T. (2004). Halofuginone inhibits angiogenesis and growth in implanted metastatic rat brain tumor model--an MRI study. Neoplasia. 6: 480-489.

  2. Afrin, S., Giampieri, F., Gasparrini, M., Forbes-Hernandez, T.Y., Varela-Lopez, A., Quiles, J.L., Mezzetti, B. and Battino, M. (2016). Chemopreventive and therapeutic effects of edible berries: A focus on colon cancer prevention and treatment. Molecules. 21: 169.

  3. Alrawi, S.J., Schiff, M., Carroll, R.E., Dayton, M., Gibbs, J.F., Kulavlat, M., Tan, D., Berman, K., Stoler, D.L. and Anderson, G.R. (2006). Aberrant crypt foci. Anticancer Res. 26: 107-119. 

  4. Arenas-Ramirez, N., Woytschak, J. and Boyman, O. (2015). Interleukin-2: Biology, design and application. Trends Immunol. 36: 763-777.

  5. Baier, P.K., Wolff-Vorbeck, G., Eggstein, S., Baumgartner, U. and Hopt, U.T. (2005). Cytokine expression in colon carcinoma. Anticancer Res. 25: 2135-2139. 

  6. Chen, G.Q., Tang, C.F., Shi, X.K., Lin, C.Y., Fatima, S., Pan, X.U., Yang, D.J., Zhang, G., Lu, A.P., Lin, S.H. and Bian, Z.X. (2015). Halofuginone inhibits colorectal cancer growth through suppression of Akt/mTORC1 signaling and glucose metabolism. Oncotarget. 6: 24148-24162. 

  7. Dunzendorfer, U., Ohlenschlager, G. and Zahradnik, H.P. (1981). 13,14-Dihydro-15-keto prostaglandin F2 alpha and haptoglobin in the serum of patients with urogenital tumors. Onkologie. 4: 10-16.

  8. Gavish, Z., Pinthus, J.H., Barak, V., Ramon, J., Nagler, A., Eshhar, Z. and Pines, M. (2002). Growth inhibition of prostate cancer xenografts by halofuginone. Prostate. 51: 73-83.

  9. Grudzien, M.M., Low, P.S., Manning, P.C., Arredondo, M., Belton, R.J. and Nowak, A. (2010). The antifibrotic drug halofuginone inhibits proliferation and collagen production by human leiomyoma and myometrial smooth muscle cells. Fertil Steril. 93: 1290-1298.

  10. Gupta, A.K. and Schoen, R.E. (2009). Aberrant crypt foci: are they intermediate endpoints of colon carcinogenesis in humans?. Curr Opin Gastroenterol. 25:59-65.

  11. Hayden, M.S. and Ghosh, S. (2014). Regulation of NF-kB by TNF family cytokines. Semin Immunol. 26: 253-266.

  12. Jin, C., Jia, Y., Jin, C., Dong, H., Cheng, P., Zhou, J., Wang, Y., Zheng, B. and Liu, F. (2014). Therapeutic effect of Halofuginone on ITP mice by regulating the differentiation of Th cell subsets. Int immunopharmacol. 18: 213-216. 

  13. Jordan, M.C. and Zeplin, P.H. (2012). Local inhibition of angiogenesis by halofuginone coated silicone materials. J Mater Sci Mater Med. 23: 1203-1210.

  14. Kangwan, N., Kim, Y.J., Han, Y.M., Jeong, M., Park, J.M. and Hahm, K.B. (2016). Concerted actions of ameliorated colitis, aberrant crypt foci inhibition and 15-hydroxyprostaglandin dehydrogenase induction by sonic hedgehog inhibitor led to prevention of colitis-associated cancer. Int J Cancer. 138: 1482-1493. 

  15. Khan, R., Khan, A.Q., Lateef, A., Rehman, M.U., Tahir, M., Ali, F., Hamiza, O.O., and Sultana, S. (2013). Glycyrrhizic acid suppresses the development of precancerous lesions via regulating the hyperproliferation, inflammation. angiogenesis and apoptosis in the colon of Wistar rats. PLoS One 8: e56020.

  16. Kristiansen, E. (1996). The role of aberrant crypt foci induced by the two heterocyclic amines 2-amino-3-methyl-    imidazo[4,5jJquinoline (IQ) and 2-amino- 1 -methyl-6-phenyl-imidazo[4,5b]pyridine (PhIP) in the development of colon cancer in mice. Cancer Letters. 110: 187-192

  17. Landskron, G., De la Fuente, M., Thuwajit, P., Thuwajit, C. and Hermoso, M.A. (2014). Chronic inflammation and cytokines in the tumor microenvironment. J Immunol Res. 2014: Article ID 149185.

  18. Lee, S. and Margolin, K. (2011). Cytokines in cancer immunotherapy. Cancers. 3:3856-3893.

  19. Leiba, M., Cahalon, L., Shimoni, A., Lider, O., Zhorov, A.Z., Hecht, I., Sela, U., Vlodavsky, I. and Nagler, A. (2006). Halofuginone inhibits NF-kappaB and p38 MAPK in activated T cells. J Leukoc Biol. 80: 399-406. 

  20. Leiba, M., Jakubikova, J., Klippel, S.., Mitsiades, C.S., Hideshima, T., Tai, Y.T., Leiba, A., Pines, M., Richardson, P.G., Nagler, A. and Anderson, K.C. (2012). Halofuginone inhibits multiple myeloma growth in vitro and in vivo and enhances cytotoxicity of conventional and novel agents. Brit J Haematol. 157: 718-731.

  21. Liang, J., Zhang, B., Shen, R.W., Liu, J.B., Gao, M.H., Li, Y., Li, Y.Y. and Zhang, W. (2013). Preventive effect of halofuginone on concanavalin A-induced liver fibrosis. PLoS One. 8: e82232. 

  22. Lin, WW. and Karin, M. (2007). A cytokine-mediated link between innate immunity, inflammation, and cancer. J Clin Invest. 117: 11175-1183.

  23. Mayne, S.T. (2003). Antioxidant nutrients and chronic disease: use of biomarkers of exposure and oxidative stress status in epidemiologic research. J Nutr. 133: 933-940.

  24. Morishita, Y., Yoshimi, N., Kawabata, K., Matsunaga, K., Sugic, S., Tanaka, T. and Mori, H. (1997). Regressive effects of various chemopreventive agents on azoxymethane-induced aberrant crypt foci in the rat colon. Jpn J Cancer Res. 88: 815-820. 

  25. Muthu, R., Selvaraj, N. and Vaiyapuri, M. (2015). Anti-inflammatory and proapoptotic effects of umbelliferone in colon carcinogenesis. Hum Exp Toxicol pii: 0960327115618245.

  26. Ness, R.D. (2004). Rodents, in Exotic Animal Formulary. ED: Carpenter JW, Elsevier Saunders, Philadelphia, Pennsylvania, USA, pp. 377-410. 

  27. Pines, M., Vlodavsky, I. and Nagler, A. (2000). Halofuginone: From veterinary use to human therapy. Drug Develop Res. 50: 371-378. 

  28. Raju, J. (2008). Azoxymethane-induced rat aberrant crypt foci: Relevance in studying chemoprevention of colon cancer. World J Gastroenterol. 14: 6632-6635. 

  29. Tache, S., Peiffer, G., Millet, A.S. and Corpet, D.E. (2000). Carrageenan gel and aberrant crypt foci in the colon of conventional and human flora-associated rats. Nutr Cancer. 37: 193-198.

  30. Wang, X. and Lin, Y. (2008). Tumor necrosis factor and cancer, buddies or foe. Acta Pharmacol Sin. 29: 1275-1288. 

  31. Wargovich, M.J., Brown, V.R. and Morris, J. (2010). Aberrant crypt foci: The case for inclusion as a biomarker for colon cancer. Cancers (Basel). 2: 1705-1716. 
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