Triflavin, a 7.5-kDa
cysteine-rich
polypeptide purified from Trimeresurus flavoviridis
snake venom, belongs to a family of RGD-containing
peptides, termed
disintegrins, that have been isolated from the
venoms of various vipers and shown to be potent inhibitors of platelet aggregation. The interaction of
tumor cells with extracellular matrices such as
fibronectin,
vitronectin, and
collagen has been shown to be mediated through a family of
cell surface receptors that specifically recognize an
arginine-glycine-aspartic acid (RGD) sequence within each adhesive
protein. In this study, we show that
triflavin dose-dependently inhibited adhesion of human cervical
carcinoma (HeLa) cells to extracellular matrices (ECMs; i.e.,
fibronectin,
fibrinogen, and
vitronectin). On the other hand,
triflavin exerted a limited inhibitory effect on cell adhesion to
laminin and
collagen (type I and IV). On a molar basis,
triflavin is approximately 800 times more potent than
Gly-Arg-Gly-Asp-Ser (
GRGDS) at inhibiting cell adhesion. When immobilized on plate,
triflavin significantly promoted HeLa cell adhesion, and this attachment was inhibited by
GRGDS. Furthermore,
FITC-conjugated
triflavin bound to cells in a saturable manner and its binding was inhibited by
GRGDS. In addition,
triflavin did not affect [3H]
thymidine uptake of HeLa cells during a 3-day incubation. These results suggest that
triflavin probably binds to
integrin receptors expressed on HeLa cell surface via its RGD sequence within its molecule, thereby inhibiting the adhesion of extracellular matrices to HeLa cells.