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Saxatilin suppresses tumor-induced angiogenesis by regulating VEGF expression in NCI-H460 human lung cancer cells.

Abstract
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.
AuthorsYoon-Jung Jang, Dong Seok Kim, Ok-Hee Jeon, Doo-Sik Kim
JournalJournal of biochemistry and molecular biology (J Biochem Mol Biol) Vol. 40 Issue 3 Pg. 439-43 (May 31 2007) ISSN: 1225-8687 [Print] Korea (South)
PMID17562297 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Disintegrins
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Vascular Endothelial Growth Factors
  • saxatilin
Topics
  • Cell Line, Tumor
  • Cell Proliferation (drug effects)
  • Cells, Cultured
  • Disintegrins (metabolism, pharmacology)
  • Endothelial Cells (cytology, drug effects, metabolism)
  • Enzyme-Linked Immunosorbent Assay
  • Fluorescent Antibody Technique
  • Gene Expression (drug effects)
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit (metabolism)
  • Immunoblotting
  • Lung Neoplasms (genetics, metabolism, pathology)
  • Neovascularization, Pathologic (metabolism)
  • Reverse Transcriptase Polymerase Chain Reaction
  • Vascular Endothelial Growth Factors (genetics, metabolism)

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