Suramin inhibits proliferation and DNA synthesis in transitional carcinoma cell lines.
Suramin is polysulfonated naphthylurea which has a broad range of antitumor activity. The mechanism of action of suramin is not completely understood, although it is known to inhibit enzymes in all cellular compartments, inhibit steroidogenesis and interfere with ligand-receptor binding. Suramin's large molecular size and negative charge should make it poorly absorbed through the bladder mucosa, a desired characteristic for an intravesical chemotherapeutic agent. We examined the ability of suramin to inhibit thymidine uptake and decrease cellular proliferation in 4 transitional cell carcinoma cell lines grown in vitro to determine if suramin might be a new candidate drug of treatment for patients with superficial bladder cancer. Suramin inhibited cellular proliferation of all cell lines tested (MBT2, T24, RT4 and TCCSUP) in a dose-dependent fashion. Fifty per cent inhibition of cellular proliferation compared with controls was seen with suramin concentrations of 250 to 400 micrograms/ml. by, at most, 5 to 9 days of exposure. The cell line RT4 was the cell line most sensitive to the growth inhibitory effect of suramin, with 50% growth inhibition compared with controls achieved after 3 days' exposure to a suramin concentration of 100 micrograms/ml. Suramin inhibited DNA synthesis in a dose-dependent fashion, as measured by thymidine uptake, in 3 of the 4 cell lines tested (MBT2, T24, and RT4). Suramin inhibited thymidine uptake by TCCSUP in a dose-dependent fashion, but did not achieve statistical significance.
Walther
M M
MM
Urologic Oncology Section, National Cancer Institute, Bethesda, Maryland 20892.
Trahan
E E
EE
Cooper
M
M
Venzon
D
D
Linehan
W M
WM
D000818:Animals; D002295:Carcinoma, Transitional Cell / Q000378:metabolism* / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004273:DNA, Neoplasm / Q000096:biosynthesis*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D051379:Mice; D013498:Suramin / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000473:pathology*
D004273:DNA, Neoplasm; D013498:Suramin; D013936:Thymidine