DOI QR코드

DOI QR Code

Effect of Deep Sea Water on Phase I, Phase II and Ornithine Decarboxylase.

Phase I, phase II 효소 및 ornithine decarboxylase에 미치는 해양심층수의 영향

  • Shon, Yun-Hee (Regional Innovation System, Intractable Diseases Research Center, Dongguk University) ;
  • Kim, Mee-Kyung (Regional Innovation System, Intractable Diseases Research Center, Dongguk University) ;
  • Jang, Jung-Sun (Regional Innovation System, Intractable Diseases Research Center, Dongguk University) ;
  • Jung, Eun-Jung (Department of Pharmacology, College of Medicine, Dongguk University) ;
  • Nam, Kyung-Soo (Department of Pharmacology, College of Medicine, Dongguk University)
  • 손윤희 (동국대학교 지역연고산업진흥사업단, 난치병한양방치료연구센터) ;
  • 김미경 (동국대학교 지역연고산업진흥사업단, 난치병한양방치료연구센터) ;
  • 장정선 (동국대학교 지역연고산업진흥사업단, 난치병한양방치료연구센터) ;
  • 정은정 (동국대학교 의과대학 약리학교실) ;
  • 남경수 (동국대학교 의과대학 약리학교실)
  • Published : 2008.03.31

Abstract

Deep sea water was tested for cancer chemopreventive activity by measuring the activities of ${\beta}-$ naphthoflavone $({\beta}-NF)-induced$ cytochrome P 450 1A2 (CYP 1A2), quinone reductase (QR) and glutathione-S-transferase (GST), glutathione (GSH) levels, and ornithine decarboxylase (ODC) activity. The in vitro incubation of rat liver microsome with deep sea water (a hardness range of $100{\sim}1,000$) showed a hardness-dependent inhibition of CYP 1A2 activity. QR and GST activities were induced about $1.1{\sim}1.2$ fold with the treatment of deep sea water in murine hepatoma Hepa 1clc7 cells. In addition GSH levels were increased $1.3{\sim}1.4$ fold in a hardness range of $100{\sim}1,000$. The deep sea water showed 20.3 and 35.0% inhibition of 12-O- tetradecanoylphorbol-13-a-cetate (TPA)-induced ODC activity at hardness 800 and 1,000, respectively. Therefore, deep sea water is worth further investigation with respect to cancer chemoprevention or therapy.

동해에서 취수한 해양심층수의 암예방 효능을 얄아보고자 암발생 억제물질의 생화학적 표식자(biochemical markers)인 CYP 1A2 활성, phase II 효소인 QR과 GST의 활성, GSH 함량 및 ODC 활성에 미치는 영향을 살펴보았다. 해양심층수는 암의 개시단계(initiation)를 유발시키는 것으로 알려진 CYP 1A2 활성을 경도의존적으로 저해시켰다. 해양심층수를 Hepa 1clc7 세포에 경도별$(100{\sim}1,000)$로 처리하였을 때 phase II 생체 해독효소인 QR과 GST의 활성은 최대 20%의 증가를 나타내었고, 외부의 독성물질이나 대사산물로부터 세포를 보호하는 역할을 하는 GSH의 함량은 $26{\sim}40%$의 증가를 나타내었다. 그리고 발암과정의 촉진/진행단계에 관여하는 ODC의 활성은 해양심층수의 경도 800과 1,000에서 20%와 35%의 저해율을 나타내었으며, 경도 1,000을 처리한 군에서는 양성대조군인 DFMO와 같은 저해율을 나타내었다. 그러므로 본 연구 결과에 의하면 동해 해양심층수는 발암과정과 관련된 개시 및 촉진/진행단계를 저해시켜 암예방 효능을 나타낼 것으로 사료된다.

Keywords

References

  1. Boyland, E. and L. F. Chasseaud. 1969. The role of glutathione and glutathione S-transferase in mercapturic acid biosynthesis. Adv. Enzymol. Ralat. Areas Mol. Biol. 32, 173-219.
  2. Chesis, P. L., D. E. Levin, M. T. Smith, L. Ernster and B. N. Ames. 1984. Mutagenicity of quinones: pathways of metabolic activation and detoxification. Proc. Natl. Acad. Sci. USA 81, 1696-1700. https://doi.org/10.1073/pnas.81.6.1696
  3. Feith, D. J., S. Origanti, P. L. Shoop, S. Sass-Kuhn and L. M. Shantz. 2006. Tumor suppressor activity of ODC antizyme in MEK-driven skin tumorigenesis. Carcinogenesis 27, 1090-1098. https://doi.org/10.1093/carcin/bgi343
  4. Firozi, P. F., M. L. Bondy, A. A. Sahin, P. Chang, F. Lukmanji, E. S. Singletary, M. M. Hassan and D. Li. 2002. Aromatic DNA adducts and polymorphisms of CYP 1A1, NAT2, and GSTM1 in breast cancer. Carcinogenesis 23, 301-306. https://doi.org/10.1093/carcin/23.2.301
  5. Gerhauser, C., M. You, J. Liu, R. M. Moriarty, M. Hawthorne, R. G. Mehta, R. C. Moon and J. M. Pezzuto. 1997. Cancer chemopreventive potential of sulforamate, a novel analogue of sulforaphane that induces phase II drug-metabolizing enzymes. Cancer Res. 57, 272-278.
  6. Griffith, O. W. 1980. Determination of glutathione and glutathione disulfide using glutathione reductase and 2-vinylpyridine. Anal. Biochem. 106, 207-212. https://doi.org/10.1016/0003-2697(80)90139-6
  7. Guo, Y., J. Zhao, J. Sawicki, S. A. Peralta and T. G. O'Brien. 1999. Conversion of C57Bl/6 mice from a tumor promotion-resistant to a -sensitive phenotype by enhanced ornithine decarboxylase expression. Mol. Carcinog. 26,32-36. https://doi.org/10.1002/(SICI)1098-2744(199909)26:1<32::AID-MC4>3.0.CO;2-E
  8. Habig, W. H., M. H. Pabst and W. B. Jakoby. 1974. Glutathione S-transferase; the first enzymatic step mercapturic acid formation. J. Biol. Chem. 249, 7130-7139.
  9. Jung, D. H., H. J. Kim and H. I. Park. 2004. A study on the behavior of flexible riser for upwelling deep ocean water by a numerical method. J. Ocean Eng. Tech. 18, 15-22.
  10. Kim, S. M., S. H. Ryu, H. D. Cho, S. S. Kim, J. H. Kim and J. S. Kim. 1998. Screening for Koreanean vegetables with anticarcinogenic enzyme inducing activity using cell culture system. Korean J. Food Sci. Nutr. 3, 277-281.
  11. Kimata, H., H. Tai, K. Nakagawa, Y. Yokoyama, H. Nakajima and Y. Ikegami. 2002. Improvement of skin symptoms and mineral imbalance by drinking deep sea water in patients with atopic eczema/dermatitis syndrome (AEDS). Acta Medica (Hradec Kralove). 45, 83-84.
  12. Kingsnorth, A. N., W. W. King, K. A. Diekema, P. P. McCann, J. S. Ross and R. A. Malt. 1983. Inhibition of ornithine decarboxylase with 2-difluoromethylornithine: Reduced incidence of dimethylhydrazine- induced colon tumors in mice. Cancer Res. 43, 2545-2549.
  13. Lan, L., C. Trempus and S. K. Gilmour. 2000. Inhibition of ornithine decarboxylase (ODC) decreases tumor vascularization and reverse spontaneous tumors in ODC/Ras transgenic mice. Cancer Res. 60, 5696-5703.
  14. Manson, M. M., P. B. Farmer, A. Gescher and W. P. Steward. 2005. Innovative agents in cancer prevention. Recent Results Cancer Res. 166, 257-275. https://doi.org/10.1007/3-540-26980-0_17
  15. Meister, A. and M. E. Anderson. 1983. Glutathione. Annu. Rev. Biochem. 52, 711-760. https://doi.org/10.1146/annurev.bi.52.070183.003431
  16. Mitchell, J. R., J. A. Hinson and S. D. Nelson. 1976. Glutathione and drug induced tissue lesions: metabolism and function. pp. 357-367, In Arias, I. M. and W.B. Jakoby (eds.), Glutathiones, Raven Press., New York.
  17. Miyamura, M., S. Yoshioka, A. Hamada, D. Takuma, J. Yokota, M. Kusunose, S. Kyotani, H. Kawakita, K. Odani, Y. Tsutsui and Y. Nishioka. 2004. Difference between deep seawater and surface seawater in the preventive effect of atherosclerosis. Biol. Pharm. Bull. 27, 1784-1787. https://doi.org/10.1248/bpb.27.1784
  18. Pegg, A. E. 1986. Recent advances in the biochemistry of polyamines in eukaryotes. Biochem. J. 234, 249-262. https://doi.org/10.1042/bj2340249
  19. Pohl, R. J. and J. R. Fouts. 1980. A rapid method for assaying the metabolism of 7-ethoxyresorufin by microsomal subcellular fractions. Anal. Biochem. 107, 150-155. https://doi.org/10.1016/0003-2697(80)90505-9
  20. Prochaska, H. J. and A. B. Santamarina. 1988. Direct measurement of NAD(P)H: Quinone reductase from cells cultured in microtiter wells: A screening assay for anticarcinogenic enzyme inducer. Anal. Biochem. 169, 328-336. https://doi.org/10.1016/0003-2697(88)90292-8
  21. Rodrigues, A. D. and R. A. Prough. 1991. Induction of cytochromes P450 1A1 and P450 1A2 and measurement of catalytic activities. Methods Enzymol. 206, 423-431. https://doi.org/10.1016/0076-6879(91)06111-F
  22. Singh, A., S. P. Singh and R. Bamezai. 1996. Modulatory influence of chlorophyllin on the mouse skin papollomagenesis and xenobiotic detoxification system. Carcinogenesis 17, 1459-1463. https://doi.org/10.1093/carcin/17.7.1459
  23. Spencer, S. R., C. A. Wilczak and P. Talalay. 1990. Induction of glutathione transferase and NAD(P)H: quinone reductase by fumaric acid derivatives in rodent cells and tissues. Cancer Res. 50, 7871-7875.
  24. Yang, C. S., Y. Y. Tu, D. R. Koop and M. J. Coon. 1985. Metabolism of nitrosamines by purified rabbit liver cytochrome P-450 isozymes. Cancer Res. 45, 1140-1145.
  25. Zhang, Y., T. W. Kensler, C. G. Cho, G. H. Posner and P. Talalay. 1994. Anticarciongenic activities of sulforaphane and structurally related synthetic norbornyl isothiocyanates. Proc. Natl. Acad. Sci. (USA) 91, 3147-3150. https://doi.org/10.1073/pnas.91.8.3147
  26. Zhang, Y. and P. Talalay. 1994. Anticarcinogenic activities of organic isothiocyanates: chemistry and mechanisms. Cancer Res. 54, 1976s-1981s.

Cited by

  1. Suppression of cancer progression and metastasis in HT-29 human colorectal adenocarcinomas by deep sea water vol.18, pp.1, 2013, https://doi.org/10.1007/s12257-012-0543-y
  2. Effect of yogurt containing deep sea water on health-related serum parameters and intestinal microbiota in mice vol.98, pp.9, 2015, https://doi.org/10.3168/jds.2015-9492