Suramin blocks binding of interleukin-4 to its receptors on human tumor cells and interleukin-4-induced mitogenic response.
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.
Laboratory of Molecular Tumor Biology, FDA, Bethesda, MD 20892-4555, USA.
P
P
Leland
N
N
Obiri
B B
BB
Aggarwal
R K
RK
Puri
D015703:Antigens, CD / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D002850:Chromatography, Gel; D006801:Humans; D015847:Interleukin-4 / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology*; D008024:Ligands; D018123:Receptors, Interleukin / Q000378:metabolism*; D019948:Receptors, Interleukin-4; D013498:Suramin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D000970:Antineoplastic Agents; D008024:Ligands; D018123:Receptors, Interleukin; D019948:Receptors, Interleukin-4; D015847:Interleukin-4; D013498:Suramin