A peptide derived from alpha-fetoprotein inhibits the proliferation induced by estradiol in mammary tumor cells in culture.
This study was aimed to obtain additional information on the activity of a cyclized 9-amino acid peptide (cP) containing the active site of alpha fetoprotein, which inhibits the estrogen-stimulated proliferation of tumor cells in culture and of xenografts in immunodeficient mice. Breast cancer cells cultured in the presence of 2 nM estradiol were exposed to cP for different periods and their proliferation, estradiol binding parameters, clustering tendency and expression of E-cadherin and p21Cip1 were analyzed by biochemical and cell biology methods. The proliferation of MCF7 cells was significantly decreased by the addition of 2 microg/ml cP to the medium. cP did not increase cell death rate nor alter the number of binding sites for estradiol nor the endogenous aromatase activity of MCF7 cells. cP also decreased the proliferation of estrogen-dependent ZR75-1 cells but had no effect on estrogen-independent MDA-MB-231 cells. An increased nuclear p21Cip1 expression detected after cP treatment suggests that cP slows MCF7 cell proliferation via this regulator. We propose that cP could represent a novel breast cancer therapeutic agent whose mechanism of action is different from that of tamoxifen or of inhibitors of aromatase.
Sierralta
Walter D
WD
Laboratorio de Ultrastructuras, INTA-Universidad de Chile, Santiago 7830489, Chile. wsierra@uchile.cl
Epuñan
Maria J
MJ
Reyes
José M
JM
Valladares
Luis E
LE
Andersen
Thomas T
TT
Bennett
James A
JA
Jacobson
Herbert I
HI
Pino
Ana M
AM
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D042361:Mammary Glands, Human / Q000187:drug effects*; D051379:Mice; D008819:Mice, Nude; D010455:Peptides / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays; D000509:alpha-Fetoproteins / Q000737:chemistry / Q000494:pharmacology*
D000970:Antineoplastic Agents; D050759:Cyclin-Dependent Kinase Inhibitor p21; D010455:Peptides; D000509:alpha-Fetoproteins; D004958:Estradiol