Suramin-induced growth inhibition and insulin-like growth factor-I binding blockade in human breast carcinoma cell lines: potentially related events.
Suramin, a polyanionic drug used in the treatment of trypanosomiasis and onchocerciasis, inhibits growth factor-induced mitogenesis in several human tumours. We have investigated the effect of suramin on human breast cancer cell lines (HBCCL). By cell counts and thymidine incorporation we found that 50 to 400 micrograms/ml suramin inhibits the proliferation of HBCCL in a dose-dependent and reversible fashion (ID50 approximately 200 micrograms/ml for MCF-7 and MDA-MB 231). Radioreceptor and affinity cross-linking assays showed that suramin was also able to reduce the binding of insulin-like growth factor I (IGF-I) to its receptor (40-50% inhibition at 100 micrograms/ml). Our results indicate that the drug does not affect the IGF-I receptor (IGF-I-R), but binds directly to the IGF-I peptide. In conclusion, the strict correlation observed between suramin inhibition of proliferation and IGF-I binding on HBCCL suggests a possible therapeutic role for this molecule as an antineoplastic drug in human breast tumours.
Ravera
F
F
Department of Experimental Pharmacology, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
Miglietta
L
L
Pirani
P
P
Ferrini
S
S
Favoni
R E
RE
D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008938:Mitosis / Q000187:drug effects; D011485:Protein Binding; D017526:Receptor, IGF Type 1 / Q000187:drug effects / Q000378:metabolism*; D017451:Receptors, Somatomedin / Q000032:analysis; D013498:Suramin / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D017451:Receptors, Somatomedin; D013498:Suramin; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1