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Anti‐insulin‐like growth factor‐I activity of a novel polysulphonated distamycin A derivative in human lung cancer cell lines
Author(s) -
De Cupis Alessandra,
Ciomei Marina,
Pirani Paolo,
Ferrera Alessandra,
Ardizzoni Andrea,
Favoni Roberto Enrico
Publication year - 1997
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0700937
Subject(s) - cell culture , cell growth , insulin like growth factor , receptor , growth factor , endocrinology , a549 cell , medicine , radioimmunoassay , cell , microbiology and biotechnology , chemistry , biology , biochemistry , genetics
1 The purpose of this study was to investigate the antiproliferative effect and the modulation of the mitogenic insulin‐like growth factor‐I (IGF‐I) system by FCE 26644 and FCE 27784, two polyanionic sulphonated distamycin A derivative compounds, on two human non‐small cell lung cancer (N‐SCLC) cell lines. 2 For cell growth studies the colorimetric MTT and the thymidine incorporation assays were performed; the presence of IGF‐I and IGF‐binding proteins in conditioned media was revealed by radioimmunoassay and Western ligand blot, respectively. Variations at the IGF‐I‐receptor level were tested by binding studies on cell monolayers. 3 A significant concentration‐and time‐dependent cytostatic activity of FCE 26644 (IC 50 ∼200 μg ml −1 at 72 h) compared to its analogue FCE 27784 (IC 50 >8OO μg ml −1 ) was observed in both cell lines studied. The IGF‐I‐stimulated proliferation of the IGF‐I‐responsive A549 cell line was abolished by 24 h of FCE 26644 treatment whereas FCE 27784 was inactive. FCE 26644 increased (4 to 6 fold) the secretion of IGF‐I‐like material and reduced the IGF‐I binding (IC 50 >100 μg ml −1 ) in both A549 and Ca‐Lu‐1 cell lines. FCE 26644 (100 μg ml −1 ) did not affect the K D (∼0.5 nM) but reduced the B max and the number of receptor sites (50%). 4 Our findings demonstrate that the ability to down‐regulate the cell proliferation of N‐SCLC cell lines, shown by FCE 26644, depends at least partially, on interference with the ‘IGF‐I mitogenic system’.