Suramin interferes with interleukin-6 receptor binding in vitro and inhibits colon-26-mediated experimental cancer cachexia in vivo.

Abstract

Neoplastic diseases are frequently associated with metabolic changes collectively known as cancer cachexia. The presence of cachexia complicates therapeutic intervention and is an impor- tant cause of death in cancer patients. At present there is no effective treatment for cachexia. Recently, the involvement of interleukin-6 (IL-6) in the wasting of colon-26 adenocarci- noma-bearing mice was demonstrated. The research presented here establishes an anticachectic role for the experimental drug suramin, since it partially blocks (up to 60%) the catabolic effects associated with the growth of this tumor in vivo. Sura- min prevents the binding of IL-6 to its cell surface receptor subunits, as demonstrated by radioreceptor binding assay and affinity crosslinking experiments. Furthermore, the uptake of radioactive IL-6 by the liver is significantly reduced in suramin- treated mice. On the other hand, the drug is 10-fold less potent in inhibiting the binding of tumor necrosis factor-a to indicator cell line in vitro and fails to block liver uptake of this cytokine in vivo. Collectively, these results suggest that sura- min inhibits cancer-associated wasting, in part by interfering with the binding of IL-6 to its receptor. Whether suramin in- hibits the action ofother factors /cytokines that may also participate in colon-26-mediated cachexia is not yet known. (J. Clin. Invest.