Anti-insulin-like growth factor-I activity of a novel polysulphonated distamycin A derivative in human lung cancer cell lines.

Abstract

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 (IC50 approximately 200 micrograms ml-1 at 72 h) compared to its analogue FCE 27784 (IC50 > 800 micrograms 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 (IC50 > 100 micrograms ml-1) in both A549 and Ca-Lu-1 cell lines. FCE 26644 (100 micrograms ml-1) did not affect the KD (approximately 0.5 nM) but reduced the Bmax 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'.

• Authors: A de Cupis, M Ciomei, P Pirani, A Ferrera, A Ardizzoni, R E Favoni
• Journal: British journal of pharmacology (Br J Pharmacol) Vol. 120 Issue 3 Pg. 537-43 (Feb 1997) ISSN: 0007-1188 [Print] England
• PMID: 9031761 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Culture Media, Conditioned
• DNA, Neoplasm
• Distamycins
• FCE 26644
• FCE 27784
• Insulin-Like Growth Factor Binding Proteins
• Insulin-Like Growth Factor I
• stallimycin

Topics

• Antineoplastic Agents (pharmacology)
• Blotting, Western
• Carcinoma, Non-Small-Cell Lung (metabolism, pathology)
• Cell Division (drug effects)
• Culture Media, Conditioned
• DNA, Neoplasm (biosynthesis)
• Distamycins (pharmacology)
• Humans
• Insulin-Like Growth Factor Binding Proteins (metabolism)
• Insulin-Like Growth Factor I (antagonists & inhibitors, metabolism)
• Lung Neoplasms (metabolism, pathology)
• Radioimmunoassay
• Tumor Cells, Cultured