tailieunhanh - Báo cáo Y học: Growth inhibition of mammalian cells by eosinophil cationic protein

Eosinophil cationic protein (ECP), one of the major components of basic granules of eosinophils, is cytotoxic to tracheal epithelium. However, the extent of this e ect on other cell types has not been evaluatedin study, we evaluated the e ect of ECP on 13 mammalian cell lines. ECP inhibited the growth of several cell lines including those derived from carcinoma and leukemia in a dose-dependent manner. | Eur. J. Biochem. 269 307-316 2002 FEBS 2002 Growth inhibition of mammalian cells by eosinophil cationic protein Takashi Maeda1 Midori Kitazoe1 Hiroko Tada1 Rafael de Llorens2 David S. Salomon3 Masakazu Ueda4 Hidenori Yamada1 and Masaharu Seno1 1 Department of Bioscience and Biotechnology Faculty of Engineering Graduate School of Natural Science and Technology Okayama University Japan 2Department of Biology Faculty of Sciences University of Girona Spain 3Tumor Growth Factor Section Basic Research Laboratory National Cancer Institute National Institutes of Health Bethesda MD USA Department of Surgery Keio University School of Medicine Tokyo Japan Eosinophil cationic protein ECP one of the major components of basic granules of eosinophils is cytotoxic to tracheal epithelium. However the extent of this effect on other cell types has not been evaluated in vitro. In this study we evaluated the effect of ECP on 13 mammalian cell lines. ECP inhibited the growth of several cell lines including those derived from carcinoma and leukemia in a dose-dependent manner. The IC50 values on A431 cells MDA-MB-453 cells HL-60 cells and K562 cells were estimated to be w 1-5 M. ECP signifcantly suppressed the size of colonies of A431 cells and decreased K562 cells in G1 G0 phase. However there was little evidence that ECP killed cells in either cell line. These effects of ECP were not enhanced by extending its N-terminus. Rhodamine B isothiocyanate-labeled ECP started to bind to A431 cells after h and accumulated for up to 24 h indicating that specifc affinity for the cell surface may be important. The affinity of ECP for heparin was assessed and found to be reduced when tryptophan residues one of which is located at a position in the catalytic subsite of ribonuclease in ECP were modified. The growth-inhibitory effect was also attenuated by this modification. These results suggest that growth inhibition by ECP is dependent on cell type and is cytostatic. Keywords cell cycle colony .