• Title/Summary/Keyword: saxatilin

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Saxatilin, a Snake Venom Disintegrin, Suppresses TNF-α-induced Ovarian Cancer Cell Invasion

  • Kim, Dong-Seok;Jang, Yoon-Jung;Jeon, Ok-Hee;Kim, Doo-Sik
    • BMB Reports
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    • v.40 no.2
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    • pp.290-294
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    • 2007
  • Saxatilin is a disintegrin known to inhibit tumor progression in vivo and in vitro. The role of saxatilin in cancer cell invasion was examined by a modified Boyden chamber assay in MDAH 2774 human ovarian cancer cell line. Saxatilin (50 nM) significantly inhibited cancer cell invasion induced by tumor necrosis factor-$\alpha$ (TNF-a$\alpha$). Saxatilin also reduced MMP-9 mRNA levels in cancer cells in a dosedependent manner. In addition, TNF-$\alpha$-induced MMP-9 activity was reduced by the treatment of saxatilin. These results indicate that transcriptional regulation of MMP-9 is an important mechanism for the tumor suppressive effects of saxatilin in MDAH 2774 human ovarian cancer cells.

NMR Structural Studies on Novel Disintegrin, Saxatilin from Gloydius saxatilis Venom

  • Shin, Joon;Lee, Dong-Hee;Hong, Sung-Yu;Chung, Kwang-Hoe;Kim, Doo-Sik;Lee, Weon-Tae
    • Journal of the Korean Magnetic Resonance Society
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    • v.11 no.1
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    • pp.10-23
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    • 2007
  • A new disintegrin protein named saxatilin was purified from Korean snake venom (Gloydius saxatilis). Saxatilin is a 73 residue small ploypeptide, which has a primary recognition motif in extracellular matrix, Arg-Gly-Asp (RGD) sequence. Data from inhibition activity assay for the ${\alpha}_v{\beta}_3$ integrin showed that saxatilin showed about 5000-fold higher activity than those of RGD peptides, suggesting that RGD sequence may not be sufficient to induce full cellular function of this site. The solution structures calculated from NMR data were well converged for backbone atoms except RGD loop. The structure revealed that most of tight turns are stabilized by medium range NOE contacts and the RGD motif is located far from the rigid core of the C-terminal domain. The three-dimensional fold and biological function of saxatilin are discussed with those of salmosin, which is a disintegrin protein derived from Agkistrodon halys brevicaudus.

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Saxatilin Suppresses Tumor-induced Angiogenesis by Regulating VEGF Expression in NCI-H460 Human Lung Cancer Cells

  • Jang, Yoon-Jung;Kim, Dong-Seok;Jeon, Ok-Hee;Kim, Doo-Sik
    • BMB Reports
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    • v.40 no.3
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    • pp.439-443
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    • 2007
  • Tumor growth and metastasis are dependent on angiogenesis, and endothelial cell invasion and migration are apparent means of regulating tumor progression. We report here that saxatilin, a snake venom-derived disintegrin, suppresses the angiogenesis-inducing properties of NCI-H460 human lung cancer cells. Culture supernatants of NCI-H460 cells are able to induce human umbilical vascular endothelial cell (HUVEC) invasion and tube formation. However, treatment of the cancer cells with saxatilin resulted in reduced angiogenic activity of the culture supernatant. This suppressed angiogenic property was found to be associated with the level of vascular endothelial growth factor (VEGF) in the culture supernatant. Further experimental evidence indicated that saxatilin inhibits VEGF production in NCI-H460 cells by affecting hypoxia induced factor-1$\alpha$ (HIF-1$\alpha$) expression via the Akt pathway.

Effect of methanol feed rate on the production of saxatilin by recombinant Pichia pastoris

  • Min, Cheol-Gi;Park, Hong-U;Jeong, Gwang-Hui
    • 한국생물공학회:학술대회논문집
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    • 2000.11a
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    • pp.376-379
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    • 2000
  • The methylotrophic yeast Pichia pastoris is one of the best host for the production of foreign proteins because of the presence of the strong AOX1 promoter induced by methanol. Methanol feeding induces the protein production and provides energy sources for the host cells. However, excess methanol inhibits the growth of host cells, while an insufficient methanol lead to poor growth and protein production. We have used various controled methanol feeding strategies to obtain the maximum proteins.

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