Suramin interferes with auto/paracrine insulin-like growth factor I-controlled proliferative loop on human lung cancer cell lines.
Human non-small cell lung cancer (N-SCLC), a common malignancy generally unmanageable by conventional cytotoxic chemotherapy, represents a major world health burden. Suramin, a polyanionic drug which appears to interfere with growth-factor/receptor interaction, has recently been shown to be cytostatic for small cell lung cancer cells; it may also be effective for N-SCLC. As insulin-like growth factor I (IGF-I) is a known progression agent for N-SCLC, we have examined the effects of suramin on the 'IGF-I system' in a panel of human N-SCLC cell lines. Colorimetric and thymidine incorporation assays were used to assess cell chemosensitivity whereas a radio-receptor assay was employed to evaluate IGF-I/receptor binding. Suramin reversibly reduced, in a concentration- and time-dependent manner, the growth of each N-SCLC cell line examined either cultured in serum-containing or serum-free medium. Furthermore, suramin caused a concentration-related inhibition of labeled IGF-I peptide specific binding on all cell lines studied. Suramin caused a significant reduction in the Bmax values with only weak variations in the affinity constants (Kd). We hypothesize that suramin interference with IGF-I mitogenic activity is a pathway by which this drug produces its effect in vitro. These data indicate further studies on the mechanism of action and pharmacology of suramin in vivo are warranted.
Department of Experimental Pharmacology, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
R E
RE
Favoni
F
F
Ravera
P
P
Pirani
A
A
Ardizzoni
D
D
Noonan
A
A
de Cupis
D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism; D001667:Binding, Competitive; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D005562:Formazans / Q000737:chemistry; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000187:drug effects* / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D008934:Mitogens / Q000009:adverse effects; D011869:Radioligand Assay; D013498:Suramin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D013778:Tetrazolium Salts / Q000737:chemistry; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured
D005562:Formazans; D008934:Mitogens; D013778:Tetrazolium Salts; C079782:MTT formazan; D013498:Suramin; D007334:Insulin-Like Growth Factor I; D004247:DNA; D013936:Thymidine