Inhibitory effect of salmosin, a Korean snake venom-derived disintegrin, on the integrin alphav-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 alphav monoclonal antibody at 8 microg 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 alphav. 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 alphav monoclonal antibody, anti-integrin alphavbeta3 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 alphav-mediated cell survival.
Chung
Kwang-Hoe
KH
Cardiovascular Research Institute and BK21 Project for Medical Sciences, Yonsei University College of Medicine, Seoul 120-752, Korea.
Kim
Sung-Hoon
SH
Han
Kyu-Yeon
KY
Sohn
Young-Doug
YD
Chang
Soo-Ik
SI
Baek
Kwang-Hyun
KH
Jang
Yangsoo
Y
Kim
Doo-Sik
DS
Kang
In-Cheol
IC
D017209:Apoptosis / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003435:Crotalid Venoms / Q000494:pharmacology*; D006801:Humans; D039564:Integrin alphaV / Q000187:drug effects*; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D003435:Crotalid Venoms; D039564:Integrin alphaV; C115393:salmosin