DOI QR코드

DOI QR Code

Preventive Effect of Hydrazinocurcumin on Carcinogenesis of Diethylnitrosamine-induced Hepatocarcinoma in Male SD Rats

  • Zhao, Ji-An (Department of Hepatobiliary Surgery, The First Affilliated Hospital, Hebei Medical University) ;
  • Peng, Li (Department of Hepatobiliary Surgery, The Fourth Affiliated Hospital, Hebei Medical University) ;
  • Geng, Cui-Zhi (Department of Breast Clinics Center, The Fourth Affiliated Hospital, Hebei Medical University) ;
  • Liu, Yue-Ping (Department of Pathology, The Fourth Affiliated Hospital, Hebei Medical University) ;
  • Wang, Xu (Department of Pathology, The Fourth Affiliated Hospital, Hebei Medical University) ;
  • Yang, Hui-Chai (Department of Pathology, The Fourth Affiliated Hospital, Hebei Medical University) ;
  • Wang, Shi-Jie (Department of Endoscopy, The Fourth Affiliated Hospital, Hebei Medical University)
  • Published : 2014.03.01

Abstract

The purpose of the present study was to evaluate the preventive effects of hydrazinocurcumin (HZC) on diethylnitrosamine (DEN)-induced hepatocarcinogenesis in a male Sprague Dawley (SD) rat model. One hundred and twenty male SD rats used in this study were divided into six groups. Those receiving DEN with curcumin (CUR) or HZC were studied compared with the DEN-alone group. The study demonstrated that DEN induced severe histological and immunohistochemical changes in liver tissues, significantly increasing the levels of liver marker enzymes (alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), ${\gamma}$-glutamyltransferase (GGT) and total bilirubin level (TBL)). The hepatocarcinoma incidences were 100.0%, 36.7% and 20.0% in the DEN-alone, DEN-CUR and DEN-HZC groups, respectively. Although macroscopic and microscopic features suggested that both CUR and HZC were effective in inhibiting DEN-induced hepatocarcinogenesis, HZC was exerted a stronger influence. Immunohistochemical analysis with PCNA demonstrated significantly differences among the groups (all P < 0.05). Taken together, the results suggested application of CUR and HZC could prevent the occurrence of carcinogenesis and HZC may be a more potent compound for prevention of DEN-induced hepatocarcinogenesis in rats than CUR.

Keywords

References

  1. Yildirim Y, Ozyilkan O, Bilezikci B, et al (2008).Lack of influence of cyclooxygenese-2 expression in hepatocellular carcinomas on patient survival. Asian Pac J Cancer Prev, 9, 295-8.
  2. Al-Rejaie SS, Aleisa AM, Al-Yahya AA, et al (2009). Progression of diethylnitrosamine-induced hepatic carcinogenesis in carnitine-depleted rats. World J Gastroenterol, 15, 1373-80. https://doi.org/10.3748/wjg.15.1373
  3. Anand P, Kunnumakkara AB, Newman RA, et al (2007). Bioavailability of curcumin: problems and promises. Mol Pharm, 4, 807-18. https://doi.org/10.1021/mp700113r
  4. Appiah-Opong R, de Esch I, Commandeur JN, et al (2008). Structure-activity relationships for the inhibition of recombinant human cytochromes P450 by curcumin analogues. Eur J Med Chem, 43, 1621-31. https://doi.org/10.1016/j.ejmech.2007.10.034
  5. Bulle F, Mavier P, Zafrani ES, et al (1990). Mechanism of gamma-glutamyl transpeptidase release in serum during intrahepatic and extrahepatic cholestasis in the rat: a histochemical, biochemical and molecular approach. Hepatology, 11, 545-50. https://doi.org/10.1002/hep.1840110404
  6. Dai XZ, Yin HT, Sun LF, et al (2013). Potential therapeutic efficacy of curcumin in liver cancer. Asian Pac J Cancer Prev, 14, 3855-9. https://doi.org/10.7314/APJCP.2013.14.6.3855
  7. Devasena T, Rajasekaran KN, Menon VP (2002). Bis-1, 7-(2-hydroxyphenyl)-hepta-1, 6-diene-3, 5-dione (a curcumin analog) ameliorates DMH-induced hepatic oxidative stress during colon carcinogenesis. Pharmacol Res, 46, 39-45. https://doi.org/10.1016/S1043-6618(02)00043-9
  8. Farazi PA, DePinho RA (2006). Hepatocellular carcinoma pathogenesis: from genes to environment. Nat Rev Cancer, 6, 674-87. https://doi.org/10.1038/nrc1934
  9. Gayathri R, Priya DK, Gunassekaran GR, et al (2009). Ursolic acid attenuates oxidative stress-mediated hepatocellular carcinoma induction by diethylnitrosamine in male Wistar rats. Asian Pac J Cancer Prev, 10, 933-8.
  10. Greaves P, Irisarri E, Monro AM (1986). Hepatic foci of cellular and enzymatic alteration and nodules in rats treated with clofibrate or diethylnitrosamine followed by phenobarbital: their rate of onset and their reversibility. J Natl Cancer Inst, 76, 475-84.
  11. Hasegawa R, Takahashi S, Imaida K, et al (1991). Agedependent induction of preneoplastic liver cell foci by 2-acetylaminofluorene, Phenobarbital andacetaminophen in F344 rats initially treated with diethylnitrosamine. Jpn J Cancer Res, 82, 293-97. https://doi.org/10.1111/j.1349-7006.1991.tb01845.x
  12. Huang TS, Lee SC, Lin JK (1991). Suppression of c-Jun/AP-1 activation by an inhibitor of tumor promotion in mouse fibroblast cells. Proc Natl Acad Sci USA, 88, 5292-96. https://doi.org/10.1073/pnas.88.12.5292
  13. Ishida J, Ohtsu H, Tachibana Y, et al (2002). Antitumor agents. Part 214: synthesis and evaluation of curcumin analogues as cytotoxic agents. Bioorg Med Chem, 10, 3481-87. https://doi.org/10.1016/S0968-0896(02)00249-3
  14. Kang JS (2012). Increased expression of epithelial cell adhesion molecule (EpCAM) in rat hepatic tumors induced by diethylnitrosamine. Asian Pac J Cancer Prev, 13, 3627-30. https://doi.org/10.7314/APJCP.2012.13.8.3627
  15. Kelloff GJ, Lieberman R, Steele VE, et al (1999). Chemoprevention of prostate cancer: concepts and strategies. Eur Urol, 35, 342-50. https://doi.org/10.1159/000019906
  16. Kern MA, Sch neweiss MM, Sahi D, et al (2004). Cyclooxygenase-2 inhibitors suppress the growth of human hepatocellular carcinoma implants in nude mice. Carcinogenesis, 25, 1193-99. https://doi.org/10.1093/carcin/bgh110
  17. Kumada T, Nakano S, Takeda I, et al (1997). Patterns of recurrence after initial treatment in patients with small hepatocellular carcinoma. Hepatology, 25, 87-92. https://doi.org/10.1002/hep.510250116
  18. Lee YK, Park SY, Kim YM (2009). Regulatory effect of the AMPK-COX-2 signaling pathway in curcumin-induced apoptosis in HT-29 colon cancer cells. Ann N Y Acad Sci, 1171, 489-94. https://doi.org/10.1111/j.1749-6632.2009.04699.x
  19. Llorente Izquierdo C, Mayoral R, Flores JM, et al (2011). Transgenic mice expressing cyclooxygenase-2 in hepatocytes reveal a minor contribution of this enzyme tochemical hepatocarcinogenesis. Am J Pathol, 178, 1361-73. https://doi.org/10.1016/j.ajpath.2010.11.074
  20. Marx JJM (1996). Toxicology of the blood: Pathophysiology, toxicological pathology and mechanistic aspects, In: Toxicology Principles and Applicants. Edited by Niesink JM, Vries J, Hollinger MA, pp.817-837.
  21. Mehta K, Pantazis P, McQueen T, et al (1997). Antiproliferative effect of curcumin (diferuloylmethane) against human breast tumor cell lines. Anticancer Drugs, 8, 470-81. https://doi.org/10.1097/00001813-199706000-00010
  22. Muller-Decker K (2011). Cyclooxygenase-dependent signaling is causally linked to non-melanoma skin carcinogenesis: pharmacological, genetic, and clinical evidence. Cancer Metastasis Rev, 30, 343-61. https://doi.org/10.1007/s10555-011-9306-z
  23. Nagano H (2010). Treatment of advanced hepatocellular carcinoma: intraarterial infusion chemotherapy combined with interferon. Oncology, 78, 142-47. https://doi.org/10.1159/000315243
  24. Nair KG, Deepadevi KV, Arun P, et al (1998). Toxic effect of systemic administration of low doses of the plasticizer di- (2-ethyl hexyl) phthalate [DEHP] in rats. Indian J Exp Biol, 36, 264-72.
  25. Okuda H (2007). Hepatocellular carcinoma development in cirrhosis. Best Pract Res Clin Gastroenterol, 21, 161-73.
  26. Park TJ, Kim HS, Byun KH, et al (2001). Sequential changes in hepatocarcinogenesis induced by diethylnitrosamine plus thioacetamide in Fischer 344 rats: induction of gankyrin expression in liver fibrosis, pRB degradation in cirrhosis, and methylation of p16 (INK4A) exon 1 in hepatocellular carcinoma. Mol Carcinog, 30, 138-50. https://doi.org/10.1002/mc.1022
  27. Plummer SM, Holloway KA, Manson MM, et al (1999). Inhibition of cyclo-oxygenase 2 expression in colon cells by the chemopreventive agent curcumin involvesinhibition of NF-kappaB activation via the NIK/IKK signalling complex. Oncogene, 18, 6013-20. https://doi.org/10.1038/sj.onc.1202980
  28. Rathore R, Jain JP, Srivastava A, et al (2008). Simultaneous determination of hydrazinocurcumin and phenol red in samples from rat intestinal permeability studies: HPLC method development and validation. J Pharm Biomed Anal, 46, 374-80. https://doi.org/10.1016/j.jpba.2007.09.019
  29. Selvam C, Jachak SM, Thilagavathi R, et al (2005). Design, synthesis, biological evaluation and molecular docking of curcumin analogues as antioxidant, cyclooxygenase inhibitory and anti-inflammatory agents. Bioorg Med Chem Lett, 15, 1793-7. https://doi.org/10.1016/j.bmcl.2005.02.039
  30. Shim JS, Kim DH, Jung HJ, et al (2002). Hydrazinocurcumin, a novel synthetic curcumin derivative, is a potent inhibitor of endothelial cell proliferation. Bioorg Med Chem, 10, 2987-92. https://doi.org/10.1016/S0968-0896(02)00129-3
  31. Singh BN, Singh BR, Sarma BK, et al (2009). Potential chemoprevention of N-nitrosodiethylamine-induced hepatocarcinogenesis by polyphenolics from Acacia nilotica bark. Chem Biol Interact, 181, 20-8. https://doi.org/10.1016/j.cbi.2009.05.007
  32. Sivaramakrishnan V, Shilpa PN, Praveen Kumar VR, et al (2008). Attenuation of N-nitrosodiethylamine-induced hepatocellular carcinogenesis by a novel flavonol-Morin. Chem Biol Interact, 171, 79-8. https://doi.org/10.1016/j.cbi.2007.09.003
  33. Sreepriya M, Bali G (2005). Chemopreventive effects of embelin and curcumin against N-nitrosodiethylamine/phenobarbitalinduced hepatocarcinogenesis in Wistar rats. Fitoterapia, 76, 549-55. https://doi.org/10.1016/j.fitote.2005.04.014
  34. Taras D, Blanc JF, Rullier A, et al (2007). Pravastatin reduces lung metastasis of rat hepatocellular carcinoma via a coordinated decrease of MMP expression and activity. J Hepatol, 46, 69-6. https://doi.org/10.1016/j.jhep.2006.06.015
  35. Tessitore L, Costelli P, Bonetti G, et al (1993). Cancer cachexia, malnutrition, and tissue protein turnover in experimental animals. Arch Biochem Biophys, 306, 52-8. https://doi.org/10.1006/abbi.1993.1479
  36. Theise ND, Curado MP, Franceschi S (2010). Hepatocellular carcinoma. In: Bosman FT, Carneiro F, Hruban RH, Theise ND, eds. WHO Classification of Tumors of the Digestive System. Lyon, France: IARC Press: 205-16.
  37. Verburg KM, Maziasz TJ, Weiner E, et al (2001). Cox-2-specific inhibitors: definition of a new therapeutic concept. Am J Ther, 8, 49-4. https://doi.org/10.1097/00045391-200101000-00009
  38. Wang X, Zhang Y, Zhang X, et al (2012). The curcumin analogue hydrazinocurcumin exhibits potent suppressive activity on carcinogenicity of breast cancer cells via STAT3 inhibition. Int J Oncol, 40, 1189-95.
  39. Wang YX, Gao JX, Wang XY, et al (2012). Antiproliferative effects of selective cyclooxygenase-2 inhibitor modulated by nimotuzumab in estrogen-dependent breast cancer cells. Tumour Biol, 33, 957-66. https://doi.org/10.1007/s13277-012-0324-4
  40. Yao DF, Dong ZZ, Yao DB, et al (2004). Abnormal expression of hepatoma-derived gamma-glutamyltransferase subtyping and its early alteration forcarcinogenesis of hepatocytes. Hepatobiliary Pancreat Dis Int, 3, 564-70.

Cited by

  1. Pu-erh Tea Powder Preventive Effects on Cisplatin-Induced Liver Oxidative Damage in Wistar Rats vol.15, pp.17, 2014, https://doi.org/10.7314/APJCP.2014.15.17.7389
  2. Hepatoprotective Effects of Curcumin Against Diethyl Nitrosamine Induced Hepatotoxicity in Albino Rats vol.16, pp.1, 2015, https://doi.org/10.7314/APJCP.2015.16.1.103
  3. Protective Role of Selenium and High Dose Vitamin E against Cisplatin - Induced Nephrotoxicty in Rats vol.16, pp.16, 2015, https://doi.org/10.7314/APJCP.2015.16.16.6877
  4. A novel curcumin analogue is a potent chemotherapy candidate for human hepatocellular carcinoma vol.12, pp.5, 2016, https://doi.org/10.3892/ol.2016.5126