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해양심층수의 cytochrome P450 1A1, aromatase 및 MMP-9 활성 억제 효과

Effect of Deep Sea Water on Cytochrome P450 1A1, Aromatase and MMP-9.

  • 손윤희 (동국대학교 지역연고산업진흥사업단, 난치병한양방치료연구소) ;
  • 김미경 (동국대학교 지역연고산업진흥사업단) ;
  • 남경수 (동국대학교 지역연고산업진흥사업단, 동국대학교 의과대학 약리학교실)
  • Shon, Yun-Hee (Regional Innovation System, Intractable Disease Research Center) ;
  • Kim, Mee-Kyung (Regional Innovation System, Dongguk University) ;
  • Nam, Kyung-Soo (Regional Innovation System, Department of Pharmacology, College of Medicine, Dongguk University)
  • 발행 : 2008.04.30

초록

동해 해양심층수의 유방암예방 효능과 전이에 미치는 영향을 알아보기 위해 cytochrome P450 1A1 활성과 aromatase 활성 및 유방암세포의 침윤성, 이와 관련된 MMP-9 의 활성과 그 단백질 발현에 미치는 영향을 조사하였다. 해양심층수는 체내외의 여러 화학물질을 체내에서 활성화시켜 발암이나 돌연변이 등을 유발시키는 것으로 알려진 cytochrome P450 1A1을 경도의존적으로 저해시켰다. 또한 호르몬 의존성 유방암의 진행에 관여하는 aromatase의 활성도 경도의존적으로 저해시켰다($5.6{\sim}51.9%$). 해양심층수 처리에 의해 사람유방암세포인 MDA-MB-231 세포의 침윤성은 $73.7{\sim}29.4%$로 감소하였으며, 세포의 침윤시 작용하는 단백질 분해 효소인 MMP-9의 활성과 단백질 발현도 경도의존적으로 억제되었다. 따라서 해양심층수는 유방암 예방과 전이관련의 더 많은 연구에 의해 유방암 예방과 전이 억제작용을 증명할 수 있을 것으로 보인다.

Deep sea water from the East sea was tested for breast cancer chemoprevention and metastasis by measuring the activities of cytochrome P450 1A1 and aromatase, invasiveness, and activity and expression of matrix metalloproteinase (MMP)-9 in breast MDA-MB-231 cancer cell. 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 7,12-dimethylbenz[a]anthracene (DMBA)-induced cytochrome P450 1A1 activity. Deep sea water showed 27.1, 45.4 and 51.9% inhibition of microsomal aromatase activity at the hardness of 600, 800 and 1,000, respectively. In addition deep sea water inhibited not only the invasiveness of 12-O-tetradecanoylphorbol-13-acetate (TPA)-treated MDA-MB-231 cells through matrigel-coated membrane in a hardness-dependent manner but also the activity and expression of MMP-9 in MDA-MB-231 cell.

키워드

참고문헌

  1. Benaud, C., R. B. Dickson and E. W. Thompson. 1998. Roles of the matrix metalloproteinases in mammary gland development and cancer. Breast Cancer Res. Treat. 50, 97-116 https://doi.org/10.1023/A:1006061115909
  2. Brodie, A., Q. Lu and J. Nakamura. 1997. Aromatase in the normal breast and breast cancer. J. Steroid Biochem. Mol. Biol. 61, 281-286 https://doi.org/10.1016/S0960-0760(97)80024-6
  3. Brown, P., R. Bioxidge, E. Anderson and A. R. Howlett. 1993. Expression of activated gelatinase in human breast carcinoma. Clin. Exp. Metast. 11, 183-189 https://doi.org/10.1007/BF00114976
  4. Chang, C. and Z. Werb. 2001. The many faces of metalloproteases: cell growth, invasion, angiogenesis and metastasis. Trends Cell Biol. 11, s37-s43 https://doi.org/10.1016/S0962-8924(01)02122-5
  5. 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
  6. Forrester, L. M., J. D. Hayes, R. Millis, D. Barnes, A. L. Harris, J. J. Schlager, G. Powis and C. R. Wolf. 1990. Expression of glutathione S-transferases and cytochrome P450 in normal and tumor breast tissue. Carcinogenesis 11, 2163-2170 https://doi.org/10.1093/carcin/11.12.2163
  7. Huang, Q., H. M. Shen and C. N. Ong. 2004. Inhibitory effect of emodin on tumor invasion through suppression of activator protein-1 and nuclear factor-kappaB. Biochem. Pharmacol. 68, 361-371 https://doi.org/10.1016/j.bcp.2004.03.032
  8. Jiang, J., V. Slivova and D. Sliva. 2006. Ganoderma lucidum inhibits proliferation of human breast cancer cells by down-regulation of estrogen receptor and NF-kappaB signaling. Int. J. Oncol. 29, 695-703
  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. Korean Ocean Engineers 18, 15-22
  10. Kermorgant, S., T. Aparicio, V. Dessirier, M. J. Lewin and T. Lehy. 2001. Hepatocyte growth factor induces colonic cancer cell invasiveness via enhancer motility and protease overproduction. Evidence for PI3 kinase and PKC involvement. Carcinogenesis 22, 1035-1042 https://doi.org/10.1093/carcin/22.7.1035
  11. 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
  12. Nangia-Makker, P., T. Raz, L. Tait, V. Hogan, R. Fridman and A. Raz. 2007. Galectin-3 cleavage: a novel surrogate marker for matrix metalloproteinase activity in growing breast cancers. Cancer Res. 67, 11760-11768 https://doi.org/10.1158/0008-5472.CAN-07-3233
  13. National Cancer Center. 2007. Annual report of the Korean central cancer registry program. pp. 17, Ministry of Health and Welfare, Seoul
  14. Pike, M. C., D. V. Spicer, L. Dahmoush and M. F. Press. 1993. Estrogens, progestogens, normal breast cell proliferation, and breast cancer risk. Epidemiol. Rev. 15, 17-35 https://doi.org/10.1093/oxfordjournals.epirev.a036102
  15. Platet, N., C. Prevostel, D. Derocq, D. Joubert, H. Rochefort and M. Garcia. 1998. Breast cancer invasiveness: correlation with protein kinase C activity and differential regulation by phorbol ester in estrogen receptor-positive and -negative cells. Int. J. Cancer 75, 750-756 https://doi.org/10.1002/(SICI)1097-0215(19980302)75:5<750::AID-IJC14>3.0.CO;2-A
  16. 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
  17. Riedel, F., K. Gotte, J. Schwalb, W. Bergler and K. Hormann. 2000. Expression of 92-kDa type IV collagenase correlate with angiogenic markers and poor survival in head and neck squamous cell carcinoma. Int. J. Oncol. 17, 1099-1105
  18. 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
  19. Simpson, E. R., M. S. Mahendroo, G. D. Means, M. W. Kilgore, M. M. Hinshelwood, S. Graham-Lorence, B. Amarneh, Y. Ito, C. R. Fisher and M. D. Michael. 1994. Aromatase cytochrome P450, the enzyme responsible for estrogen biosynthesis. Endocr. Rev. 15, 342-355
  20. Song, I. H. 2004. Cancer metastasis and metastasis supressors. Korean J. Gastroenterology 43, 1-7
  21. Sreenath, T., L. M. Matrisian, W. Stetler-Stevenson, S. Gattoni-Celli and R. O. Pozzatti. 1992. Expression of matrix metalloproteinases genes in transformed rat cell lines of high and low metastatic potential. Cancer Res. 52, 4942-4947
  22. Sridar, C., U. M. Kent, L. M. Notley, E. M. Gillam and P. F. Hollenberg. 2002. Effect of tamoxifen on the enzymatic activity of human cytochrome CYP2B6. J. Pharmacol. Exp. Ther. 301, 945-952 https://doi.org/10.1124/jpet.301.3.945
  23. Stetler-Stevenson, W. G. 1990. Type IV collagenases in tumor invasion and metastasis. Cancer Metastasis Rev. 9, 289-303 https://doi.org/10.1007/BF00049520
  24. Thompson, E. A. Jr. and P. K. Siiteri. 1974. Utilization of oxygen and reduced nicotinamide adenine dinucleotide phoshpate by human placental microsomes during aromatization of androstenedione. J. Biol. Chem. 249, 5364-5372
  25. Woessner, J. F. Jr. 1991. Matrix metalloproteinases and their inhibitors in connective tissue remodeling. FASEB. J. 5, 2145-2154 https://doi.org/10.1096/fasebj.5.8.1850705
  26. Yoon, H. S., S. H. Hong, H. J. Kang, X. Xu and S. H. Ahn. 2003. Survival analysis and its prognostic factors after distant relapse in breast cancer patients. J. Korean Surg. Soc. 64, 101-108

피인용 문헌

  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. Mineral-enriched deep-sea water inhibits the metastatic potential of human breast cancer cell lines vol.43, pp.5, 2013, https://doi.org/10.3892/ijo.2013.2089