Suramin inhibits the stimulation of acute phase plasma protein genes by IL-6-type cytokines in rat hepatoma cells.
The cytokines, IL-1 beta, TNF-alpha, IL-6, IL-11, leukemia inhibitory factor, and ciliary neurotrophic factor, stimulate the expression of specific sets of acute phase plasma proteins in the rat hepatoma H-35 cell line. In this paper, the experimental drug suramin is shown to inhibit in a dose-dependent fashion the cell response to these cytokines, with the exception of TNF-alpha. The action of the IL-6-type cytokines is more sensitive to suramin inhibition that that of IL-1 beta. The effect of suramin is detectable within 30 min at the level of gene transcription and appears to be mediated by the impairment of receptor function and/or signal transduction, rather than by the inhibition of nucleic acid polymerases or DNA topoisomerase II. Similar analysis of human hepatoma HepG2 cells indicated a several-fold higher resistance to suramin and in inhibition that was less cytokine-specific than in H-35 cells. The data suggest that suramin has the potential not only to modulate the proliferation or differentiation of tumor cells as described previously, but also to affect a differentiated cell function. This broad pleiotropic action has to be taken into consideration when applying suramin as a therapeutic agent.
Baumann
H
H
Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, NY 14263.
Strassmann
G
G
D000209:Acute-Phase Proteins / Q000235:genetics*; D000818:Animals; D016207:Cytokines / Q000037:antagonists & inhibitors*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008114:Liver Neoplasms, Experimental; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011971:Receptors, Immunologic / Q000378:metabolism; D019947:Receptors, Interleukin-6; D013498:Suramin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D000093242:Interleukin-6 Inhibitors
D000209:Acute-Phase Proteins; D016207:Cytokines; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D019947:Receptors, Interleukin-6; D013498:Suramin; D000093242:Interleukin-6 Inhibitors