Abstract
BACKGROUND: In the past, some small peptide ligands identified by phage display technologies have successfully been used in early cancer diagnostics and therapy. In the present study, a novel CD59-binding peptide was identified and its effect on HeLa cell growth and apoptosis was investigated. METHODS: A phage display library was screened yielding a novel short peptide, sp22, that specifically binds to CD59, a protein that shows altered expression in various diseases, including cancer. The effect of ectopic sp22 administration and exogenous sp22 expression on the growth and apoptosis of HeLa cells was assessed. For the latter, we constructed and transfected a sp22-pIRES vector into HeLa cells. RESULTS: Our results show that sp22 peptides can inhibit the level of CD59 mRNA expression, down-regulate Bcl-2 expression, increase Fas and caspase-3 expression, increase the level of cytolysis, and increase the apoptosis of HeLa cells. In contrast, sp22 peptides had no effect on normal human embryonic lung (HEL) cells exhibiting a relatively low CD59 expression level. Compared to untransfected HeLa cells, exogenously sp22 expressing HeLa cells showed a reduced CD59 expression, an increased complement-mediated lysis, a decreased cellular survival ratio, and an increase in apoptotic cells. CONCLUSION: The newly identified sp22 peptide can, in a dose-dependent manner, inhibit CD59 expression. Concomitantly, sp22 can increase complement-mediated lysis and apoptosis signals. This information may be instrumental for the design of novel therapeutic strategies.