|Title:||Triflavin, an antiplatelet peptide, inhibits tumor cell-extracellular matrix adhesion through an arginine-glycine-aspartic acid-dependent mechanism||Authors:||SHEU, JOEN-RONG
|Issue Date:||1994||Source:||JOURNAL OF LABORATORY AND CLINICAL MEDICINE||Journal Volume:||v.123||Journal Issue:||n.2||Start page/Pages:||256-263||Abstract:||
The interaction of fumor cells with extracellular matrix components such as laminin, fibronectin, and collagen has been shown to be mediated through a family of cellsurface receptors that specifically recognize an arginine-glycine- asparfic acid amino acid sequence within each protein. Triflavin, a 7.5 kDa cysteine-rich polypeptide purified from Trimeresurus flavoviridis snake venom, belong to a family of arginine-glycine-aspartic acid-containing peptides termed disintegrins that have been isolated from the venoms of various vipers and shown to be potent inhibitors of platelet aggregation. In this study, we showed that triflavin inhibited adhesion of human hepatoma J-5 cells to extracellular matrices (fibronectin, vitronectin, fibrinogen , and collagen type 1) in a dose-dependent manner. On the other hand, trifiavin exeried a limited inhibitory effect on cell attachment to collagen type IV and laminin ( 40%). Triflavin is approximately 1000 times more potent than glycine-arginine-glycine- aspartic acid-serine at inhibiting cell adhesion, When immobillzed on plate, triflavin promoted J-5 cell attachment ; this attachment was inhibited by glycine-arginine-glycine-aspartic acid-serine. In addition, triflavin labeled with iodine 125 binds to j-5 cells in a saturable manner and its binding was also inhibited by glycine-arginine-glycine-aspartic acid-serine. Its Kd value was estimated to be 3.9×10-7 mol/L amd tje mi, ber pf bomdomg sotes qas arpimd 60,000 per cell. Furthermore, triflavin did not affect tritiated thymidine uptake during a 3-day incubation. These results suggest that triflavin binds by means of its arginine-glycine- aspartic acid amino acid sequence to integrin receptor expressed on the J- 5 cell surface, inhibiting the adhesion of extracellular matrices to tumor cells.#0842#
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