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.
Favoni
R E
RE
Department of Experimental Pharmacology, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
Ravera
F
F
Pirani
P
P
Ardizzoni
A
A
Noonan
D
D
de Cupis
A
A
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