Induction of Phase II Enzymes and Inhibition of Cytochrome P450 Isozymes by Chitosanoligosaccharides

  • SHON, YUN-HEE (Department of Pharmacology, College of Medicine and Intractable Disease Research Center, Dongguk University) ;
  • NAM, KYUNG-SOO (Department of Pharmacology, College of Medicine and Intractable Disease Research Center, Dongguk University)
  • Published : 2005.02.01

Abstract

Abstract The cancer chemopreventive potential of chitosanoligosaccharides was investigated by measuring the induction of quinone reductase and glutathione S-transferase activities and inhibition of cytochrome P450 1A1, 2B1, and 2E1 activities. Chitosanoligosaccharide I (1-${\kappa}$Da${\kappa}$Da) significantly induced glutathione S-transferase activity with a maximal 1.5-fold increase at 500 ${\mu}$g/ml, while chitosanoligosaccharide II (3-${\kappa}$Da${\kappa}$Da) (500 ${\mu}$g/ml) strongly induced quinone reductase (p<0.01) and glutathione S-transferase (p<0.005) activities. The in vitro incubation of rat liver microsomes with chitosanoligosaccharides I and II (2.5, 5, 50, and 500 ${\mu}$g/ml) showed a dose-dependent inhibiton of cytochrome P450 1A1, 2B1, and 2E1 activities. Chitosanoligosaccharide II was a more potent inhibitor of cytochrome P450 2B1 activity than chitosanoligosaccharide I. Accordingly, these findings suggest that chitosanoligosaccharides are potential chemopreventive agents.

Keywords

References

  1. Bandaru, S. R., V. R. Chinthalapally, R. Abraham, and K. Gary. 1993. Chemoprevention of colon carcinogenesis by organosulfur compounds. Cancer Res. 53: 3493- 3498
  2. Bogaards, J. J. P., H. Verhagen, M. I. Willems, G. van Poppel, and P. J. van Bladeren. 1994. Consumption of Brussels sprouts results in elevated a-class glutathione Stransferase levels in human blood plasma. Carcinogenesis 15: 1073- 1075 https://doi.org/10.1093/carcin/15.5.1073
  3. Burke, M. D., S. Thompson, C. R. Elcombe, J. Halpert, T. Haaparanta, and R. T. Mayer. 1985. Ethoxy-, pentoxy and benzyloxyphenoxazones and homologues: A series of substrates to distinguish between different induced cytochromes P-450. Biochem. Pharmacol. 34: 3337- 3345 https://doi.org/10.1016/0006-2952(85)90355-7
  4. Dicker, E., Y. McHugh. and A. I. Cederbaum. 1990. Increased oxidation of p-nitrophenol and aniline by intact hepatocytes isolated from pyrazole-treated rats. Biochim. Biophys. Acta 1035: 249- 256 https://doi.org/10.1016/0304-4165(90)90086-C
  5. Guengerich, F. P. 1988. Roles of cytochrome P450 enzymes in chemical carcinogenesis and cancer chemotherapy. Cancer Res. 48: 2946- 2954
  6. Guo, Z., T. J. Smith, E. Wang, K. I. Eklind, F. L. Chung, and C. S. Yang. 1993. Structure activity relationships of arylalkyl isothiocyanates for the inhibition of 4-(methylnitrosamino)1-(3-pyridyl)-l-butanone metabolism and the modulation of xenobiotic-metabolising enzymes in rats and mice. Carcinogenesis 14: 1167- 1173 https://doi.org/10.1093/carcin/14.6.1167
  7. Habig, W. H., M. J. Pabst, and W. B. lakoby. 1974. Glutathione S-transferases: The first enzymatic step in mercapturic acid formation. J. Biol. Chem. 249: 7130- 7139
  8. Hong, I. P., K. J. Hong, Y. L. Shin, and G. C. Shin. 2003. Cloning and characterization of a bifunctional cellulasechitosanase gene from Bacillus licheniformis NBL420. J. Microhiol. Biotechnol. 13: 35- 42
  9. Hong, W. K. and M. B. Sporn. 1997. Recent advances in chemopreventibn of cancer. Science 278: 1073- 1077 https://doi.org/10.1126/science.278.5340.1073
  10. Izume, M. and A. Ohtakara. 1987. Preparation of Dglucosamine oligosaccharides by the enzymatic hydrolysis of chitosan. Agric. Biol. Chem. 51: 1189- 1191 https://doi.org/10.1271/bbb1961.51.1189
  11. Jo, Y. Y., K. J. Jo, Y. L. Jin, W. J. Jung, J. H. Kuk, K. Y. Kim, T. H. Kim, and R. D. Park. 2003. Characterization of endochitosanases-producing Bacillus cereus P16. J. Microbiol. Biotechnol. 13: 960- 968
  12. Kato, H., T. Taguchi, H. Okuda, M. Kondo, and M. Takara. 1994. Antihypertensive effect of chitosan in rats and humans. J. Tradit. Chin. Med. 11: 198- 205
  13. Kensler. T. W., P. A. Egner, P. M. Dolan. J. D. Grooprnan, and B. D. Roebuck. 1987. Mechanism of protection against aflatoxin tumorigenicity in rats fed 5-(2-pyrazinyl)-4-methy1-1,2-dithiol-3-thione (oltipraz) and related 1,2-dithiol-3-thiones and 1,2-dithiol-3-thones. Cancer Res. 47: 4271-4277
  14. Kent, U. M., D. E. Mills. R. V. Rajnarayanan, W. L. Alworth, and P. F. Hollenberg. 2002. Effect of 17-alphaethynylestradiol on activities of cytochrome P450 2B (P450 2B) enzymes: Characterization of inactivation of P450s 2B1 and 2B6 and identification of metabolites. J. Pharmacol. Exp. Ther. 300: 549- 558 https://doi.org/10.1124/jpet.300.2.549
  15. Lee, J. E. and S. Safe. 2001. Involvement of a posttranscriptional mechanism in the inhibition of CYPlAl expression by resveratrol in breast cancer cells. Biochem. Pharmacol. 62: 1113- 1124 https://doi.org/10.1016/S0006-2952(01)00763-8
  16. Loizou, G. D. and J. Cocker. 2001. The effects of alcohol and diallyl sulphide on CYP2El activity in humans: A phenotyping study using chlorzoxazone. Hum. Exp. Toxicol 20: 321-327 https://doi.org/10.1191/096032701680350587
  17. Marcinkicwicz, J., A. Polewska, and J. Knapczyk. 1991. Immunoadjuvant properties of chitosan. Arch. Immunol. Ther. Exp. (Warsz) 39: 127- 132
  18. Nam, K. S., Y. R. Choi, and Y. H. Shon. 2001. Evaluation of the antimutagenic potential of chitosan oligosaccharide: Rec, Ames and Umu assays. Biotechnol. Lett. 23: 971- 975 https://doi.org/10.1023/A:1010519224254
  19. Ormrod, D. J., C. C. Holmes, and T. E. Miller. 1998. Dietary chitosan inhibits hypercholesterolemia and atherogenesis in the apolipoprotein E-deficient mouse model of atherosclerosis. Atherosclerosis 138: 329- 334 https://doi.org/10.1016/S0021-9150(98)00045-8
  20. Park, P. J., H. K. Lee, and S. K. Kim. 2004. Preparation of hetero-chitooligosaccharides and their antimicrobial activity on Vibrio parahaemolyticus. J. Microbiol Biotechnol, 14: 41-47
  21. Prochaska, H. J. and C. L. Fernandes. 1993. Elevation of serum phase II enzymes by anticarcinogenic enzyme inducers: Markers for a chemoprotected state? Carcinogenesis 14: 2441-2445
  22. Schweikl, H., J. A. Taylor, S. Kitareewan, P. Linko, D. Nagorney, and J. A. Goldstein. 1993. Expression of CYP1A1 and CYP 1A2 genes in human liver. Pharmacogenetics 3: 239- 249 https://doi.org/10.1097/00008571-199310000-00003
  23. Shon, Y. H., I. K. Park, I. S. Moon, H. W. Chang, I. K. Park, and K. S. Nam. 2002. Effect of chitosan oligosaccharide on 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced oxidative stress in mice. Biol. Pharm. Bull. 25: 1161- 1164 https://doi.org/10.1248/bpb.25.1161
  24. Shon, Y. H. and K. S. Nam. 2003. Inhibition of polyamine biosynthesis of Acanthamoeba castellanii and 12-O-tetradecanoylphorbol-13-acetate-induced ornithine decarboxylase activity by chitosanoligosaccharide. Biotechnol. Lett. 25: 701- 704 https://doi.org/10.1023/A:1023480701270
  25. Shon, Y. H., K. S. Nam, and M. K. Kim. 2004. Cancer chemopreventive potential of Scenedesmus spp. cultured in medium containing bioreacted swine urine. J. Microbiol. Biotechnol. 14: 158- 161
  26. Talalay, P., J. W. Fahey, W. D. Holtzclaw, T. Prestera, and Y. Zhang. 1995. Chemoprotection against cancer by phase II enzyme induction. Toxicol Lett. (Amst.) 82: 173- 179 https://doi.org/10.1016/0378-4274(95)03553-2
  27. Tsukada, K., T. Matsumoto, K. Aizawa, A. Tokoro, R. Naruse, S. Suzuki, and M. Suzuki. 1990. Antimetastatic and growth-inhibitory effects of N-acetylchitohexaose in mice bearing Lewis lung carcinoma. Jpn. J. Cancer Res. 81: 259-265 https://doi.org/10.1111/j.1349-7006.1990.tb02559.x
  28. Yang, C. S., T. J. Smith, and J. Y. Hong. 1994. Cytochrome P450 enzymes as targets for chemoprevention against chemical carcinogenesis and toxicity: Opportunities and limitations. Cancer Res. 54(Suppl.): 1982s- 1986s
  29. Zhang, Y., T. W. Kensler, C. G. Cho, G. H. Posner, and P. Talalay. 1994. Anticarcinogenic activities of sulforaphane and structurally related synthetic norbornyl isothiocyanates. Proc. Natl. Acad. Sci. USA 91: 3147- 3150