G. Strassmann et al., SURAMIN INTERFERES WITH INTERLEUKIN-6 RECEPTOR-BINDING IN-VITRO AND INHIBITS COLON-26-MEDIATED EXPERIMENTAL CANCER CACHEXIA IN-VIVO, The Journal of clinical investigation, 92(5), 1993, pp. 2152-2159
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.