ANTI-INSULIN-LIKE GROWTH-FACTOR-I ACTIVITY OF A NOVEL POLYSULPHONATEDDISTAMYCIN-A DERIVATIVE IN HUMAN LUNG-CANCER CELL-LINES

1 The purpose of this study was to investigate the antiproliferative e ffect and the modulation of the mitogenic insulin-like growth factor-I (IGF-I) system by FCE 26644 and FCE 27784, two polyanionic sulphonate d 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 presen ce 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 mo nolayers. 3 A significant concentration- and time-dependent cytostatic activity of FCE 26644 (IC(50)approximate to 200 mu g ml(-1) at 72 h) compared to its analogue FCE 27784 (IC50 > 800 mu g ml(-1)) was observ ed in both cell lines studied. The IGF-I-stimulated proliferation of t he 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 bindi ng (IC50 > 100 mu g ml(-1)) in both A549 and Ca-Lu-1 cell lines. FCE 2 6644 (100 mu g ml(-1)) did not affect the K-D (approximate to 0.5 nM) but reduced the B-max and the number of receptor sites (50%). 4 Our fi ndings demonstrate that the ability to down-regulate the cell prolifer ation of N-SCLC cell lines, shown by FCE 26644, depends at least parti ally, on interference with the 'IGF-I mitogenic system'.