Inhibitory effect of salmosin, a Korean snake venom-derived disintegrin, on the integrin αv-mediated proliferation of SK-Mel-2 human melanoma cells

We have investigated the inhibitory effect of salmosin on integrin-mediated human tumour cell proliferation. SK-Mel-2 human melanoma cell adhesion to denatured collagen or vitronectin was found to be significantly and statistically inhibited by salmosin in a dose-dependent manner (P<0.05). Moreover, the binding of SK-Mel-2 cells to salmosin-coated plates was specifically disrupted by anti-integrin a, monoclonal antibody at 8 mug mL(-1), but not by anti-integrin monoclonal antibody. These findings indicated that salmosin inhibited the adhesion of SK-Mel-2 cells to denatured collagen by specifically blocking integrin alpha(v). The proliferation of SK-Mel-2 cells on a denatured collagen-coated plate was statistically and significantly inhibited by salmosin induced apoptosis in a dose-dependent manner (P<0.05). Anti-integrin alpha(v) monoclonal antibody, anti-integrin alpha(v)beta(3) monoclonal antibody, and synthetic RGD peptide also suppressed SK-Mel-2 cell proliferation. Several lines of experimental evidence strongly suggested that the inhibition of SK-Mel-2 cell proliferation by salmosin was due to the induction of apoptosis via the blocking of integrin alpha(v)-mediated cell survival.