Suramin selectively inhibits carcinoma cell growth that is dependent on extracellular polyamines.
Polyamines are necessary for tumour cell growth. Inhibition of endogenous polyamine biosynthesis results in compensatory up-regulation of polyamine uptake. Here, the combined effect of suramin and the polyamine biosynthesis inhibitor alpha-difluoromethylornithine (DFMO) on human carcinoma cell proliferation was studied. Suramin selectively inhibited the growth of tumour cells made dependent on extracellular polyamines by DFMO-treatment. In an animal tumour model, low non-toxic doses of suramin resulted in a 2-fold increase in DFMO tumour growth reduction. Moreover, suramin bound strongly to polyamine-agarose and significantly inhibited polyamine uptake in DFMO-treated cells. Our results indicate that non-toxic doses of suramin augment tumour growth inhibition by DFMO, and that a combination of these well-studied anticancer drugs may represent an additional strategy for cancer treatment.
Sandgren
Staffan
S
Department of Cell and Molecular Biology, Biomedical Centre C-13, Lund University, SE-221 84 Lund, Sweden.
Belting
Mattias
M
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002277:Carcinoma / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D002846:Chromatography, Affinity; D004357:Drug Synergism; D000518:Eflornithine / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006131:Growth Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006493:Heparin / Q000378:metabolism; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D011073:Polyamines / Q000494:pharmacology*; D012685:Sepharose; D013047:Specific Pathogen-Free Organisms; D013096:Spermine / Q000378:metabolism; D013498:Suramin / Q000494:pharmacology / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured / Q000187:drug effects; D001749:Urinary Bladder Neoplasms / Q000473:pathology*; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D006131:Growth Inhibitors; D011073:Polyamines; D013096:Spermine; D013498:Suramin; D006493:Heparin; D012685:Sepharose; D000518:Eflornithine