A synthetic peptide derived from alpha-fetoprotein inhibits the estradiol-induced proliferation of mammary tumor cells in culture through the modulation of p21

Abstract

A stable cyclized 9-mer peptide (cP) containing the active site of α-alpha fetoprotein (αFP) has been shown to be effective for prevention of estrogenstimulated tumor cell proliferation in culture or of xenographt growth in immunodeficient mice. cP does not block 17β-estradiol (E2) binding to its receptors, but rather appears to interfere with intracellular processing of the signal that supports growth. To obtain insight on that mechanism we studied the effect of cP on the proliferation of MCF-7 cells in culture. Proliferation in the presence of 2μM E2 is decreased up to 40% upon addition of 2μg ml-1 cP to the medium; the presence of cP did not increase cell death. cP reduced also the proliferation of estrogen-dependent ZR75-1 cells but had no effect on autonomous MDA-MB-231 cells. cP did not modify the number of binding sites for labeled E2 or affected cell death. We detected increased nuclear p21 Cip1 immunoreactivity after cP treatment. Our results suggest that cP acts via p21Cip1 to slow the process of MCF-7 cells through the cycle. © 2008 Springer Science+Business Media, LLC.