Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Streptochlorin, a Marine Natural Product, Inhibits $NF-{\kappa}B$ Activation and Suppresses Angiogenesis In Vitro

  • Choi, In-Kwon (Chemical Genomics Laboratory, Department of Biotechnology, College of Engineering, Yonsei University) ;
  • Shin, Hee-Jae (Marine Natural Product Chemistry Laboratory, Ocean Research and Development Institute) ;
  • Lee, Hyi-Seung (Marine Natural Product Chemistry Laboratory, Ocean Research and Development Institute) ;
  • Kwon, Ho-Jeong (Chemical Genomics Laboratory, Department of Biotechnology, College of Engineering, Yonsei University)
  • Published : 2007.08.30
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Abstract

Angiogenesis is an essential step in tumor progress and metastasis. Accordingly, small molecules that inhibit angiogenesis would appear to be a promising way to cure angiogenesis-related diseases, including cancer. In the present study, we report that streptochlorin, a small molecule from marine actinomycete, exhibits a potent antiangiogenic activity. The compound potently inhibited endothelial cell invasion and tube formation stimulated with vascular endothelial cell growth factor (VEGF) at low micromolar concentrations where it showed no cytotoxicity to the cells. In addition, streptochlorin inhibited TNF-${\alpha}$-induced $NF-{\kappa}B$ activation in the newly developed cell-based reporter gene assay. These data demonstrate that streptochlorin is a new inhibitor of $NF-{\kappa}B$ activation and can be a basis for the development of novel anti-angiogenic agents.

Keywords

References

  1. Andersen, N. F., T. Standal, J. L. Nielsen, L. Heickendorff, M. Borset, F. B. Sorensen, and N. Abildgaard. 2005. Syndecan-1 and angiogenic cytokines in multiple myeloma: Correlation with bone marrow angiogenesis and survival. Br. J. Haematol. 128: 210-217 https://doi.org/10.1111/j.1365-2141.2004.05299.x
  2. Baeuerle, P. A. and T. Henkel. 1994. Function and activation of NF-$\kappa$B in the immune system. Annu. Rev. Immunol. 12: 141-179 https://doi.org/10.1146/annurev.iy.12.040194.001041
  3. Boehm, T., J. Folkman, T. Browder, and M. S. O'Reilly. 1997. Antiangiogenic therapy of experimental cancer does not induce acquired drug resistance. Nature 390: 404-407 https://doi.org/10.1038/37126
  4. Deplanque, G. and A. L. Harris. 2000. Anti-angiogenic agents: Clinical trial design and therapies in development. Eur. J. Cancer 36: 1713-1724 https://doi.org/10.1016/S0959-8049(00)00149-0
  5. Desai, S. B. and S. K. Libutti. 1999. Tumor angiogenesis and endothelial cell modulatory factors. J. Immunother. 22: 186-211 https://doi.org/10.1097/00002371-199905000-00002
  6. Folkman, J. 1995. Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat. Med. 1: 27-31 https://doi.org/10.1038/nm0195-27
  7. Giuliani, N., S. Colla, F. Morandi, and V. Rizzoli. 2005. Angiopoietin-1 and myeloma-induced angiogenesis. Leuk. Lymphoma 46: 29-33 https://doi.org/10.1080/1042-8190400001022
  8. Hideshima, T., P. L. Bergsagel, W. M. Kuehl, and K. C. Anderson. 2004. Advances in biology of multiple myeloma: Clinical applications. Blood 104: 607-618 https://doi.org/10.1182/blood-2004-01-0037
  9. Ingber, D., T. Fujita, S. Kishimoto, K. Sudo, T. Kanamaru, H. Brem, and J. Folkman. 1990. Synthetic analogues of fumagillin that inhibit angiogenesis and suppress tumour growth. Nature 348: 555-557 https://doi.org/10.1038/348555a0
  10. Jung, H. J. and H. J. Kwon. 2006. Chemical genomics with natural products. J. Microbiol. Biotechnol. 16: 651-660
  11. Jung, H. J., H. B. Lee, C. J. Kim, J. R. Rho, J. Shin, and H. J. Kwon. 2003. Anti-angiogenic activity of terpestacin, a bicyclo sesterterpene from Embellisia chlamydospora. J. Antibiot. (Tokyo) 56: 492-496 https://doi.org/10.7164/antibiotics.56.492
  12. Kim, H. J., J. H. Kim, C. H. Lee, and H. J. Kwon. 2006. Gentisyl alcohol, an antioxidant from microbial metabolite, induces angiogenesis in vitro. J. Microbiol. Biotechnol. 16: 475-479
  13. Kim, H. Y., J.-R. Kim, and H.-S. Kim. 2006. Synergistic effect of interleukin-18 on the expression of lipopolysaccharideinduced IP-10 (CXCL-10) mRNA in mouse peritoneal macrophages. J. Microbiol. Biotechnol. 16: 1605-1612
  14. Klein, S., A. R. de Fougerolles, P. Blaikie, L. Khan, A. Pepe, C. D. Green, V. Koteliansky, and F. G. Giancotti. 2002. a5b1 integrin activates an NF-$\kappa$B-dependent program of gene expression important for angiogenesis and inflammation. Mol. Cell. Biol. 22: 5912-5922 https://doi.org/10.1128/MCB.22.16.5912-5922.2002
  15. Ko, H. M., K. H. Seo, S. J. Han, K. Y. Ahn, I. H. Choi, G. Y. Koh, H. K. Lee, M. S. Ra, and S. Y. Im. 2002. Nuclear factor $\kappa$B dependency of platelet-activating factor-induced angiogenesis. Cancer Res. 62: 1809-1814
  16. Lim, J. K., H. J. Seo, E. O. Kim, M. Meydani, and J. D. Kim. 2006. Identification of anti-angiogenic and anti-cell adhesion materials from halophilic enterobacteria of the Trachurus japonicus. J. Microbiol. Biotechnol. 16: 1544-1553
  17. Malyankar, U. M., M. Scatena, K. L. Suchland, T. J. Yun, E. A. Clark, and C. M. Giachelli. 2000. Osteoprotegerin is an $\alpha$v$\beta$3-induced, NF-$\kappa$B-dependent survival factor for endothelial cells. J. Biol. Chem. 275: 20959-20962 https://doi.org/10.1074/jbc.C000290200
  18. Min, J. K., Y. M. Kim, Y. M. Kim, E. C. Kim, Y. S. Gho, I. J. Kang, S. Y. Lee, Y. Y. Kong, and Y. G. Kwon. 2003. Vascular endothelial growth factor up-regulates expression of receptor activator of NF-$\kappa$B (RANK) in endothelial cells. Concomitant increase of angiogenic responses to RANK ligand. J. Biol. Chem. 278: 39548-39557 https://doi.org/10.1074/jbc.M300539200
  19. O'Reilly, M. S., T. Boehm, Y. Shing, N. Fukai, G. Vasios, W. S. Lane, E. Flynn, J. R. Birkhead, B. R. Olsen, and J. Folkman. 1997. Endostatin: An endogenous inhibitor of angiogenesis and tumor growth. Cell 88: 277-285 https://doi.org/10.1016/S0092-8674(00)81848-6
  20. Oitzinger, W., R. Hofer-Warbinek, J. A. Schmid, Y. Koshelnick, B. R. Binder, and R. de Martin. 2001. Adenovirus-mediated expression of a mutant I$\kappa$B kinase 2 inhibits the response of endothelial cells to inflammatory stimuli. Blood 97: 1611- 1617 https://doi.org/10.1182/blood.V97.6.1611
  21. Scatena, M., M. Almeida, M. L. Chaisson, N. Fausto, R. F. Nicosia, and C. M. Giachelli. 1998. NF-$\kappa$B mediates $\alpha$v$\beta$3 integrin-induced endothelial cell survival. 141: 1083-1093 https://doi.org/10.1083/jcb.141.4.1083
  22. Shin, H. J., H. S. Jeong, H.-S. Lee, S.-K. Park, H. M. Kim, and H. J. Kwon. 2007. Isolation and structure determination of streptochlorin, an anti-proliferative agent from a marinederived Streptomyces sp. 04DH110. J. Microbiol. Biotechnol. 17: 1403-1406
  23. Shono, T., M. Ono, H. Izumi, S. I. Jimi, K. Matsushima, T. Okamoto, K. Kohno, and M. Kuwano. 1996. Involvement of the transcription factor NF-$\kappa$B in tubular morphogenesis of human microvascular endothelial cells by oxidative stress. Mol. Cell. Biol. 16: 4231-4239 https://doi.org/10.1128/MCB.16.8.4231
  24. Wang, W., J. L. Abbruzzese, D. B. Evans, L. Larry, K. R. Cleary, and P. J. Chiao. 1999. The nuclear factor-$\kappa$B RelA transcription factor is constitutively activated in human pancreatic adenocarcinoma cells. Clin. Cancer Res. 5: 119-127
  25. Watanabe, H., S. Amano, J. Yoshida, Y. Takase, S. Miyadoh, T. Sasaki, M. Hatsu, Y. Takeuchi, and Y. Komada. 1988. A new antibiotic SF2583A, 4-chloro-5-(3'-indolyl)oxazole, produced by Streptomyces. Meiji Seika Kenkyu Nenpo 27: 55-62
  26. Zakarija, A. and G. Soff. 2005. Update on angiogenesis inhibitors. Curr. Opin. Oncol. 17: 578-583 https://doi.org/10.1097/01.cco.0000183672.15133.ab