Advertisement

Molecular and Cellular Biochemistry

, Volume 310, Issue 1–2, pp 209–214 | Cite as

Prevention of N-nitrosodiethylamine-induced hepatocarcinogenesis by S-allylcysteine

  • Sivapatham Sundaresan
  • Perumal Subramanian
Article

Abstract

Chemopreventive effect of S-allylcysteine (constituent of garlic) on N-nitrosodiethylamine (NDEA)-induced hepatocarcinogenesis was evaluated in Wistar rats. Significantly decreased lipid peroxidation products (thiobarbituric acid reactive substances-TBARS and lipid hydroperoxides) with increased level of reduced glutathione, increased activities of glutathione S-transferase, and glutathione peroxidase were observed in liver of NDEA-treated rats when compared with control rats. The activities of superoxide dismutase and catalase were significantly decreased in tumor tissue when compared with control. Administration of S-allylcysteine (SAC) showed the inhibition of tumor incidence, modulated the lipid peroxidation, and increased the reduced glutathione, glutathione-dependent enzymes, superoxide dismutase, and catalase in NDEA-induced carcinogenesis. From our results, we speculate that S-allylcysteine mediates its chemopreventive effects by modulating lipid peroxidation, GST stimulation, and by increasing the antioxidants. Hence SAC prevents cells from loss of oxidative capacity in NDEA-induced hepatocarcinogenesis.

Keywords

Antioxidants Hepatocarcinogenesis Lipid peroxidation Nitrosodiethylamine S-allylcysteine 

References

  1. 1.
    Sharma RA, Farmer PB (2004) Biological relevance of adduct detection to the chemoprevention of cancer. Clin Cancer Res 10(15):4901–4912PubMedCrossRefGoogle Scholar
  2. 2.
    Leykum LK, El-Serag HB, Cornell J, Papadopoulos KP (2007) Screening for hepatocellular carcinoma among veterans with hepatitis C on disease stage, treatment received, and survival. Clin Gastroenterol Hepatol 5(4):508–512PubMedCrossRefGoogle Scholar
  3. 3.
    Poduri CD (2003) Hepatitis C virus (HCV) – a review; molecular biology of the virus, immunodiagnostics, genomic heterogeneity and the role of virus in hepatocellular carcinoma. Indian J Exp Biol 41(6):549–562PubMedGoogle Scholar
  4. 4.
    Hara A, Sakata K, Yamada Y, Kuno T, Kitaori N, Oyama T, Hirose Y, Murakami A, Tanaka T, Mori H (2005) Suppression of beta-catenin mutation by dietary exposure of auraptene, a citrus antioxidant, in N, N-diethylnitrosamine-induced hepatocellular carcinomas in rats. Oncol Rep 14(2):345–351PubMedGoogle Scholar
  5. 5.
    Sakata K, Hara A, Hirose Y, Yamada Y, Kuno T, Katayama M, Yoshida K, Zheng Q, Murakami A, Ohigashi H, Ikemoto K, Koshimizu K, Tanaka T, Mori H (2004) Dietary supplementation of the citrus antioxidant auraptene inhibits N, N-diethylnitrosamine-induced rat hepatocarcinogenesis. Oncology 6(3):244–252CrossRefGoogle Scholar
  6. 6.
    Yadav AS, Bhatnagar D (2007) Chemo-preventive effect of Star anise in N-nitrosodiethylamine initiated and phenobarbital promoted hepato-carcinogenesis. Chem Biol Interact 169:207–214Google Scholar
  7. 7.
    Moreno FS, Toledo LP, de Conti A, Heidor R, Jordão A Jr, Vannucchi H, Cardozo MT, Ong TP (2007) Lutein presents suppressing but not blocking chemopreventive activity during diethylnitrosamine-induced hepatocarcinogenesis and this involves inhibition of DNA damage. Chem Biol Interact 168(3):221–228PubMedCrossRefGoogle Scholar
  8. 8.
    Buchmann A, Schwarz M, Schmitt R, Wolf CR, Oesch F, Kunz W (1987) Development of cytochrome P-450-altered preneoplastic and neoplastic lesions during nitrosamine-induced hepatocarcinogenesis in the rat. Cancer Res 47(11):2911–2918PubMedGoogle Scholar
  9. 9.
    Cerutti PA (1985) Prooxidant states and tumor promotion. Science 227:375–381PubMedCrossRefGoogle Scholar
  10. 10.
    Leoppky RN, Li YK (1985) Nitrosamine activation and detoxification through free radicals and their derived cations. In: Neill IKO, Chen J, Bartsch H (eds) Relevance to human cancer of nitroso compounds. Tobacco and mycotoxins. IARC Scientific Publication No. 105, Lyon, pp 375–382Google Scholar
  11. 11.
    Lee BH, Lee SJ (1999) Preventive effects of mixed disulphide from dithiocarbamate and N-acetylcysteine on the genotoxicity of N-nitrosodiethylamine. J Pharm Pharmacol 51:105–109PubMedGoogle Scholar
  12. 12.
    Sengupta A, Ghosh S, Das S (2004) Modulatory influence of garlic and tomato on cyclooxygenase-2 activity, cell proliferation and apoptosis during azoxymethane induced colon carcinogenesis in rat. Cancer Lett 208(2):127–136PubMedCrossRefGoogle Scholar
  13. 13.
    Wen J, Zhang Y, Chen X, Shen L, Li GC, Xu M (2004) Enhancement of diallyl disulfide-induced apoptosis by inhibitors of MAPKs in human HepG2 hepatoma cells. Biochem Pharmacol 68(2):323–331PubMedCrossRefGoogle Scholar
  14. 14.
    Perez-Severiano F, Salvatierra-Sanchez R, Rodriguez-Perez M, Cuevas-Martinez EY, Guevara J, Limon D, Maldonado PD, Medina-Campos ON, Pedraza-Chaverri J, Santamaria A (2004) S-Allylcysteine prevents amyloid-beta peptide-induced oxidative stress in rat hippocampus and ameliorates learning deficits. Eur J Pharmacol 489(3):197–202PubMedCrossRefGoogle Scholar
  15. 15.
    Maldonado PD, Chanez-Cardenas ME, Pedraza-Chaverri J (2005) Aged garlic extract, garlic powder extract, S-allylcysteine, diallyl sulfide and diallyl disulfide do not interfere with the antibiotic activity of gentamicin. Phytother Res 19(3):252–254PubMedCrossRefGoogle Scholar
  16. 16.
    Oberley LW, Buettner GR (1979) Role of SOD in cancer. A review. Cancer Res 39:1141–1149PubMedGoogle Scholar
  17. 17.
    Amagese H, Milner JA (1993) Impact of various sources of garlic and their constituents on 7, 12 dimethylanthracene binding to cell DNA. Carcinogenesis 14:1677–1681CrossRefGoogle Scholar
  18. 18.
    Cohen LA, Zhao Z, Pittman B, Lubet R (1999) S-allylcysteine, a garlic constituent, fails to inhibit N-methylnitrosourea-induced rat mammary tumorigenesis. Nutr Cancer 35(1):58–63PubMedCrossRefGoogle Scholar
  19. 19.
    Sundaresan S, Subramanian P (2003) S-allylcysteine inhibits circulatory lipid peroxidation and promotes antioxidants in N-nitrosodiethylamine-induced carcinogenesis. Pol J Pharmacol 55:37–42PubMedGoogle Scholar
  20. 20.
    Saydam N, Kirb A, Demir O, Hazan E, Oto O, Saydam O (1997) Determination of glutathione reductase, glutathione peroxidase and glutathione - S transferase levels in human lung cancer tissues. Cancer Lett 119:13–19CrossRefPubMedGoogle Scholar
  21. 21.
    Sundaresan S, Subramanian P (2002) Evaluation of chemopreventive potential of garlic extract on N-nitrosodiethylamine-induced hepatic carcinoma in rats. Pharm Biol 40:PB067–PB072CrossRefGoogle Scholar
  22. 22.
    Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358PubMedCrossRefGoogle Scholar
  23. 23.
    Jiang ZY, Hunt JV, Wolf SP (1992) Detection of lipid hydroperoxides using the FOX method. Anal Biochem 202:384PubMedCrossRefGoogle Scholar
  24. 24.
    Ellman GL (1959) Tissue sulfhydryl groups. Arch Biochem Biophys 82:70–77PubMedCrossRefGoogle Scholar
  25. 25.
    Rotruck JT, Pope AL, Gauther HE, Swanson AB, Hafeman DC, Hoekstra WG (1973) Selenium: biochemical roles as a component of glutathione peroxidase. Science 179:588–590PubMedCrossRefGoogle Scholar
  26. 26.
    Habig WH, Pabst MJ, Jakoby WB (1974) Glutathione-S transferase, the first enzymatic step in mercapturic acid formation. J Biol Chem 249:7130–7139PubMedGoogle Scholar
  27. 27.
    Kakkar PN, Das B, Viswanathan P (1984) A modified spectrophotometric assay of Superoxide dismutase. Indian J Biochem Biophys 21:130–132PubMedGoogle Scholar
  28. 28.
    Sinha AK (1972) Colorimetric assay of catalase. Anal Biochem 47:389–394PubMedCrossRefGoogle Scholar
  29. 29.
    Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein Measurement with the folin phenol reagent. J Biol Chem 193:265–275PubMedGoogle Scholar
  30. 30.
    Balasenthil S, Rao KS, Nagini S (2002) Apoptosis induction by S-allylcysteine, a garlic constituent, during 7,12-dimethylbenz[a]anthracene-induced hamster buccal pouch carcinogenesis. Cell Biochem Funct 20(3):263–268PubMedCrossRefGoogle Scholar
  31. 31.
    Lee ES, Steiner M, Lin R (1994) Thioallyl compounds potent inhibitor of cell proliferation. Biochem Biphys Acta 1221:73–77CrossRefGoogle Scholar
  32. 32.
    Lu YP, Lou YR, Yen P, Newmark HL, Mirochnitchenko OC, Inouye M (1997) Enhanced skin carcinogenesis in transgenic mice with high expression of glutathione peroxidase. Cancer Res 57:1468–1474PubMedGoogle Scholar
  33. 33.
    Dianzani MU (1993) Lipid peroxidation and cancer. Crit Rev Oncol Haematol 15:125–147CrossRefGoogle Scholar
  34. 34.
    Hatano S, Jimenez A, Wargovich MJ (1996) Chemopreventive effect of SAC and its relationship to the detoxification enzyme glutathione S-transferase. Carcinogenesis 17:1041–1044CrossRefGoogle Scholar
  35. 35.
    Slater TF, Benedetto C, Burton GW, Cheeseman KH, Ingold KG, Nodes JT (1984) Lipid peroxidation in animal tumors. A disturbance in the control of cell division. In: Thaler-Dao H, Crarter de paulet A, Paoletti R (eds) Eicosanoids and cancer. Raven Press, New York, pp 21–29Google Scholar
  36. 36.
    Prestera T, Zhang Y, Spencer SR, Wilczak C, Talalay P (1993) The electrophilic counter attack responses: protection against neoplasia and toxicity. Adv Enzyme Regul 33:281–296PubMedCrossRefGoogle Scholar
  37. 37.
    Church S, Grant J, Ridnour L, Oberley L, Swanson P (1993) Increased manganese superoxide dismutase expression suppresses the malignant phenotype of human melanoma cells. Proc Natl Acad Sci USA 90:3113–3117PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2008

Authors and Affiliations

  1. 1.Department of Biochemistry and Biotechnology, Faculty of ScienceAnnamalai UniversityAnnamalai NagarIndia

Personalised recommendations