Suramin is synergistic with vinblastine in human colonic tumor cell lines: effect of cell density and timing of drug delivery.
Suramin is a multi-targeted antiproliferative drug developed for the treatment of African trypanosomiasis but with potential efficacy for the treatment of human cancer. Cell growth inhibition was determined in vitro for three human colonic tumor cell lines using three different doses of suramin (50, 100 and 200 microM). At the lower suramin concentration cell growth was stimulated relative to control cultures in all three cell lines. At the higher dose which is at the upper end of the tolerable dose in humans suramin reduced cell numbers by greater than 50%. Inhibition of cellular proliferation was reduced relative to increases in cell plating density. Addition of vinblastine six and to a lesser extent 72 hours post suramin (200 microM) resulted in an inhibition of cell growth and/or toxicity that exceeded that which occurred as a result of exposure to either suramin or vinblastine alone. To investigate the possible mechanism by which suramin sensitizes cells to vinblastine we determined the effect of suramin on expression of the multidrug resistance (mdr1) gene. A decrease in mdr1 mRNA was evident in one colon tumor cell line and a slight decrease detected in a second line. The results establish that suramin is effective in controlling growth in colonic tumor cells and confirms that suramin activity is synergistic with other chemotherapeutics. The effect of suramin on MDR is of potential value that needs to be more thoroughly investigated particularly in cancers such as the those of the colon that are often drug refractory.
Frommel
T O
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Department of Medicine, Loyola University, Maywood, IL 60153, USA.
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis; D000970:Antineoplastic Agents / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006801:Humans; D007700:Kinetics; D016133:Polymerase Chain Reaction; D013498:Suramin / Q000633:toxicity*; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured; D014747:Vinblastine / Q000633:toxicity*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D014747:Vinblastine; D013498:Suramin