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The Korean Society for Biotechnology and Bioengineering (한국생물공학회)
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Effect of Mulberry Extracts on Secretion of MMPs and Plasmin in U-373-MG Cells

U-373-MG 세포에서 MMPs 및 플라스민의 분비에 미치는 오디 추출물의 효과

  • Lee, Suk-Hee (Division of Biological Sciences, Research Center of Bioactive Materials, Chonbuk National University) ;
  • Kim, Hwan-Gyu (Division of Biological Sciences, Research Center of Bioactive Materials, Chonbuk National University)
  • 이숙희 (전북대학교 자연과학대학 생물과학부, 생리활성물질연구소) ;
  • 김환규 (전북대학교 자연과학대학 생물과학부, 생리활성물질연구소)
  • Published : 2008.04.29
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Abstract

In order to sprout and migrate, cells must secrete proteinases which are degrading the surrounding extracellular matrix. In this study, we examined the effect of mulberry extracts and combination of mulberry extracts and VEGF on human malignant glioma U-373-MG cells. Mulberry extracts induced the secretion of matrix metalloproteinase-9 (MMP-9) and suppressed the secretion of MMP-2 and plasmin. Mulberry extracts inhibited the VEGF-induced MMP-2, MMP-9 and plasmin secretion. It is therefore, suggested that mulberry extracts can suppress the VEGF-induced tumor angiogenesis in U-373-MG cells. Also, mulberry extracts induced the secretion of MMP-9 and plasmin through PI 3'-kinase pathway in U-373-MG cells.

본 연구에서는 U-373-MG 세포를 이용하여 오디 추출물과 VEGF에 의한 MMPs 및 플라스민의 분비에 미치는 영향을 확인하고자 하였다. U-373-MG 세포에 오디 추출물을 $100{\sim}600\;{\mu}g/mL$의 농도로 처리한 결과, MMP-2의 분비는 거의 완벽하게 억제되었고 MMP-9의 분비는 약 $1.6{\sim}5.9$배 증가하였다. 이에 비해 플라스민의 분비는 오디 추출물 농도 $500{\sim}600\;{\mu}g/mL$에서 $36%{\sim}58%$ 감소하였다. 오디 추출물과 VEGF를 병용처리한 경우, MMP-2의 분비는 VEGF만을 처리한 것과 비교하여 약 85.5% 감소하였고, MMP-9의 분비는 약 89.8% 감소하였다. 또한, U-373-MG 세포에서 오디 추출물($100\;{\mu}g/mL$)에 의한 MMP-2와 MMP-9의 분비 증가와 플라스민 분비증가는 PI 3'-kinase 경로에 의존적이었다. 본 연구 결과를 통해 오디 추출물이 VEGF의 과발현에 따른 암의 성장을 억제 조절하는데 이용될 수 있는 가능성을 확인하였다.

Keywords

References

  1. Scharrer, A. and M. Ober (1981), Anthocyanosides in the treatment of retinopathies, Klin. Monatsbl. Augenheiked. 178, 386-389 https://doi.org/10.1055/s-2008-1057228
  2. Kim, T. W., Y. B. Kwon, J. H. Lee, I. S. Yang, J. K. Youm, H. S. Lee and J. Y. Moon (1996), A study on the antidiabetic effect of mulberry fruits, Kor. J. Seric. Sci. 38, 100-107
  3. Tamura, H. and A. Yamagami (1994), Antioxidative activity of monoacylated anthocyanins isolated from muscat bailey a grape, J. Agric. Food Chem. 42, 1612-1615 https://doi.org/10.1021/jf00044a005
  4. Yoshiki, Y., K. Okubo, and K. Igarashi (1995), Chemikuminescence of anthocyanins in the presence of acetaldehyde and tert-butyl hydroperoxide, J. Biolumin. Chemilumin. 10, 335-338 https://doi.org/10.1002/bio.1170100605
  5. Park, J. C., J. S. Choi, and J. W. Choi (1995), Effect of the Fractions from the leaves, fruits, stems and roots of Cudrania tricuspidata and flavonoids on lipid peroxidation, Kor. J. Pharmacol. 26, 377-384
  6. Kim, M. H., K. C. Ko, S. H. Lim, and Y. S. Yu (1980), Study on the usability of Mulberry fruit (1) Fruit characteristics of Mulberry, Coll. of Argic. Bull. SNU. 5, 221-223
  7. Havsteen, B. (1983), Flavonoids, a class of natural products of high pharmacological potency, Biochem. Pharmacol. 32, 1141-1145 https://doi.org/10.1016/0006-2952(83)90262-9
  8. Risau, W. (1997), Mechanisms of angiogenesis, Nature 386, 671-674 https://doi.org/10.1038/386671a0
  9. Millauer, B., S. Wizigmann-Voos, H. Schnurch, R. Martinez, N. P. Moller, W. Risau, and A. Ullrich (1993), High affinity VEGF binding and developmental expression suggest FIk-1 as a major regulator of vasculogenesis and angiogenesis, Cell 72, 835-846 https://doi.org/10.1016/0092-8674(93)90573-9
  10. Pepper, M. S. (2001), Role of the matrix metalloproteinase and plasminogen activator-plasmin systems in angiogenesis, Arterioscler. Thromb. Vasc. Biol. 21, 1104-1117 https://doi.org/10.1161/hq0701.093685
  11. Lamoreaux, W. J., M. E. C. Fitzgerald, A. Reiner, K. A. Hasty, and S. T. Chares (1998), Vascular endothelial growth factor increase release of gelatinase A and decrease of tissue inhibitor of metalloproteinases by microvascular endothelial cells in vitro, Microvas. Res. 55, 29-42 https://doi.org/10.1006/mvre.1997.2056
  12. Woessner, J. F. Jr. (1994), The family of matrix metalloproteinase, Ann. N. Y. Acid. Sci. 732, 11-21 https://doi.org/10.1111/j.1749-6632.1994.tb24720.x
  13. Sounni, N. E. and A. Noel (2005), Membrane type-matrix metalloproteinases and tumor progression, Biochemie 87, 329-342 https://doi.org/10.1016/j.biochi.2004.07.012
  14. Brown, P. D. (1997), Matrix metalloproteinase inhibitors, Angiogenesis 1, 142-154 https://doi.org/10.1023/A:1018373520193
  15. Anita, E. Y., A. N. Murphy, and W. G. Stetler-Stevenson (1998), 72kDa gelatinase (gelatinase A) : strecture, activation, regulation, and substrate specificity, In Matrix metalloproteinases, W. C. Parks and R. P. Mecham, Eds., pp. 85-113, Academic Press. London. UK
  16. Dor, Y., R. Porat, and E. Keshet (2001), Vascular endothelial growth factor and vascular adjustments to perturbances in oxygen homeostasis, Am. J. Physiol. 280, 1367-1374 https://doi.org/10.1152/ajpcell.2001.280.6.C1367
  17. Neufeld, G., T. Cohen, S. Gengrinovitch, and Z. Poltorak (1999), Vascular endothelical growh factor (VEGF) and its receptor, FASEB J. 13, 9-22 https://doi.org/10.1096/fasebj.13.1.9
  18. Ferrara, N. and W. J. Henzel (1989), Pituitary specific for vascular endothelial cell, Biochem. Biophy. Res. Commu. 161, 852-858
  19. Zhang, H. T., P. Graft, P. A. Scott, M. Ziche, H. A. Weich, A. L. Harris, and R. Bicknell (1995), Enhancement of tumor growth and vascular density by transfection of vascular endothelial cell growth factor into MCF-7 human breast carcinoma cells, J. Natl. Cancer. Inst. 87, 213-219 https://doi.org/10.1093/jnci/87.3.213
  20. Plate, K. H. and W. Risau (1995), Angiogenesis in malignant gliomas, Glia 15, 339-347 https://doi.org/10.1002/glia.440150313
  21. Saeki, Y. (1994), Effect of seaweed extracts on Streptococcus sobrinus adsorption to saliva-coated hydroxyapatite, Bull. Tokyo Dent. Coll. 35, 9-15
  22. Kim, H. G. and G. Y. Koh (2000), Lipopolysacchride activates matrix metalloproteinase-2 in endotherial cells through and NF-$\kappa$ B-dependent pathway, Biophys. Res. Commu. 269, 401-405 https://doi.org/10.1006/bbrc.2000.2308
  23. Thiennu, H. and Z. Werb (2000), Matrix metalloproteinases: effectors of development and normal physiology, Genes Dev. 14, 2123-2133 https://doi.org/10.1101/gad.815400
  24. Pepper, M. S. (2001), Extracellular proteolysis and angiogenesis, Thromb. Haemost. 86, 346-355 https://doi.org/10.1055/s-0037-1616232
  25. Goldfarb, R. H., L. A. Liotta, and V. P. Terranova (1981), Cleavage of laminin by thrombin and plasmin: Alpha thrombin selectively cleaves the beta chain of laminin, Thromb. Res. 21, 663-673 https://doi.org/10.1016/0049-3848(81)90268-1
  26. He, Y., X. D. Liu, Z. Y. Chen, J. Zhu, Y. Xiong, K. Li, J. H. Dong, and X. Li (2007), Interaction between cancer cells and stromal fibroblasts is required for activation of the uPAR-uPA-MMP-2 cascade in pancreatic cancer metastasis, Clin. Cancer Res. 13, 3115-3124 https://doi.org/10.1158/1078-0432.CCR-06-2088
  27. Bergers, G., R. Brekken, G. McMahon, T. H. Vu, T. Itoh, K. Tamaki, K. Tanzawa, P. Thorpe, S. Itohara, Z. Werbrn, and D. Hanahanm (2000), Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis, Nat. Cell Biol. 2, 737-744 https://doi.org/10.1038/35036374
  28. Brekken, R. A., X. Huang, S. W. King, and P. E. Thorpe (1998), Vascular endothelial growth factor as a marker of tumor endothelium, Cancer Res. 58, 1952-1959
  29. Dewyer, N. A., V. Sood, E. M. Lynch, C. E. Luke, G. R. Jr. Upchurch, T. W. Wakefield, S. Kunkel, and P. K. Henke (2007), Plasmin inhibition increases MMP-9 activity and decreases vein wall stiffness during venous thrombosis resolution, J. Surg. Res. 142, 357-363 https://doi.org/10.1016/j.jss.2007.03.064