Fetal fetuin selectively induces apoptosis in cancer cell lines and shows anti-cancer activity in tumor animal models

Abstract

An apoptosis-inducing protein with molecular weight of 60 kDa has been purified from fetal bovine serum. The N-terminal amino acid sequence of this protein (e.g. I-P-L-D-P-V-A-G-Y-K) reveals that it is bovine fetuin, a fetal protein functioning to control embryogenesis. The apoptosis-inducing activity of fetuin is totally dependent on zinc. Depletion of zinc ion from fetuin or substitution of zinc ion by barium ion completely abolished the apoptosis-inducing activity of fetuin. Interestingly, while the fetuin isolated from fetal serum selectively induces apoptosis in cancer without affecting normal cells, the fetuin isolated from mature serum is completely inactive. This suggests that the biological activity of fetuin is under developmental regulation. In vivo, tumor animal model studies showed that fetuin enhanced survival by up to 141% in P388 leukemia animal model in mice. Fetuin was also found to inhibit prostate cancer formation in a PC-3 prostate cancer model in mice.