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Oncol Res. 1995;7(5):227-35.

Suramin blocks binding of interleukin-4 to its receptors on human tumor cells and interleukin-4-induced mitogenic response.

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Laboratory of Molecular Tumor Biology, FDA, Bethesda, MD 20892-4555, USA.


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.

[Indexed for MEDLINE]

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