       Document 0308
 DOCN  M9640308
 TI    Suramin blocks binding of interleukin-4 to its receptors on human tumor
       cells and interleukin-4-induced mitogenic response.
 DT    9604
 AU    Leland P; Obiri N; Aggarwal BB; Puri RK; Laboratory of Molecular Tumor
       Biology, FDA, Bethesda, MD; 20892-4555, USA.
 SO    Oncol Res. 1995;7(5):227-35. Unique Identifier : AIDSLINE MED/96034539
 AB    Suramin, a polysulphonated naphthylurea, has antiproliferative,
       anticancer, and anti-HIV activities and has been shown to prevent
       binding of a variety of growth factors to their respective receptors. In
       the current study we have investigated the effects of suramin on binding
       of interleukin-4 (IL-4) to its receptors and IL-4-induced biological
       response. We found that suramin prevented the binding of 125I-labeled
       IL-4 to its receptor in a dose-dependent manner. The concentration of
       suramin that caused 50% inhibition of IL-4 binding (IC50) ranged between
       55 and 70 microM. This effect was observed on two human renal cell
       carcinoma cell lines (PM-RCC and WS-RCC), a human T lymphoma cell line
       (H9), and a human premyeloid cell line (TF-1). Cross-linking experiments
       provided direct evidence that suramin prevented binding of 125I-labeled
       IL-4 to its receptors. Radiolabeled IL-4 specifically cross-linked with
       major proteins of approximately 145 and 65-70 kDa in both PM-RCC and H9
       cell lines. Suramin prevented cross-linking to both affinity
       cross-linked IL-4 binding proteins. Gel filtration results indicated
       that suramin caused aggregation of 125I-labeled IL-4. Suramin had a
       cytostatic rather than cytotoxic effect on H9 cells, and it inhibited
       IL-4-induced proliferation of TF-1 cells. These data indicate that
       suramin may be a useful drug in the abrogation of IL-4-induced effects,
       and this property should be further explored in IL-4-mediated pathologic
       states.
 DE    Antigens, CD/*METABOLISM  Antineoplastic Agents/*PHARMACOLOGY  Cell
       Division/*DRUG EFFECTS  Cells, Cultured  Chromatography, Gel  Human
       Interleukin-4/ANTAGONISTS & INHIB/*METABOLISM/*PHARMACOLOGY  Ligands
       Receptors, Interleukin/*METABOLISM  Suramin/*PHARMACOLOGY  Tumor Cells,
       Cultured  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

