SURAMIN INTERFERES WITH INTERLEUKIN-6 RECEPTOR-BINDING IN-VITRO AND INHIBITS COLON-26-MEDIATED EXPERIMENTAL CANCER CACHEXIA IN-VIVO

Neoplastic diseases are frequently associated with metabolic changes c ollectively known as cancer cachexia. The presence of cachexia complic ates therapeutic intervention and is an important cause of death in ca ncer patients. At present there is no effective treatment for cachexia . Recently, the involvement of interleukin-6 (IL-6) in the wasting of colon-26 adenocarcinoma-bearing mice was demonstrated. The research pr esented here establishes an anticachectic role for the experimental dr ug suramin, since it partially blocks (up to 60%) the catabolic effect s associated with the growth of this tumor in vivo. Suramin prevents t he binding of IL-6 to its cell surface receptor subunits, as demonstra ted by radioreceptor binding assay and affinity crosslinking experimen ts. Furthermore, the uptake of radioactive IL-6 by the liver is signif icantly reduced in suramin-treated mice. On the other hand, the drug i s approximately 10-fold less potent in inhibiting the binding of tumor necrosis factor-alpha to indicator cell line in vitro and fails to bl ock liver uptake of this cytokine in vivo. Collectively, these results suggest that suramin inhibits cancer-associated wasting, in part by i nterfering with the binding of IL-6 to its receptor. Whether suramin i nhibits the action of other factors/cytokines that may also participat e in colon-26-mediated cachexia is not yet known.