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Molecular mechanism of a novel CD59‐binding peptide sp22 induced tumor cells apoptosis
Author(s) -
Li Bing,
Gao MeiHua,
Chu XianMing
Publication year - 2012
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.24258
Subject(s) - cytolysis , apoptosis , transfection , cd59 , biology , microbiology and biotechnology , cancer cell , cell culture , cell , immune system , complement system , cytotoxic t cell , biochemistry , in vitro , immunology , cancer , genetics
Some short peptides discovered by phage display are found to be able to inhibit cancer growth and induce cancer cell apoptosis. In this study, a novel cancer‐targeting short peptide which was composed of 22 amino acids (ACHWPWCHGWHSACDLPMHPMC, abbreviated as sp22) and specifically bound to human CD59 was screened from a M13 phage display library so as to counteract tumor immune escape activity. The mechanism of exogenous sp22 peptide in inducing apoptosis of MCF‐7 cells was investigated. The results suggested that sp22 could lower CD59 expression level, downregulate Bcl‐2 expression, activate Fas and caspase‐3, and finally increase apoptotic cell numbers of MCF‐7 cells. However, sp22 had no obvious influence on normal human embryonic lung cells. In addition, the effects of endogenous sp22 gene on CD59 expression and NKM cell apoptosis were explored using the recombinant plasmid sp22‐PIRES. It showed that sp22 gene was efficiently expressed in transfected NKM cells. Compared with normal NKM cells, NKM cells transfected with sp22 displayed reduced mRNA and protein expression levels of CD59, increased sensitivity to complement‐mediated cytolysis, decreased cell survival ratio, changes of the expression of apoptosis associated proteins, increased number of apoptotic cells and the appearance of apoptotic morphology. The results suggested that sp22 protein could bind to CD59 and inhibit the expression of CD59. The cytolytic activity of complement on tumor cells strengthened and apoptosis signal was stepwise transferred which might be a potential way to kill tumor cells. J. Cell. Biochem. 113: 3810–3822, 2012. © 2012 Wiley Periodicals, Inc.