Saxatilin suppresses tumor-induced angiogenesis by regulating VEGF expression in NCI-H460 human lung cancer cells.
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.
Jang
Yoon-Jung
YJ
Department of Biochemistry, College of Science, Yonsei University, Seoul 120-749, Republic of Korea.
Kim
Dong Seok
DS
Jeon
Ok-Hee
OH
Kim
Doo-Sik
DS
D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D019483:Disintegrins / Q000378:metabolism / Q000494:pharmacology*; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D015151:Immunoblotting; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042442:Vascular Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism*
D019483:Disintegrins; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042442:Vascular Endothelial Growth Factors; C459080:saxatilin