Calcium-pterin suppresses mitogen-induced tryptophan degradation and neopterin production in peripheral blood mononuclear cells.
Antitumor activity of a calcium-pterin suspension has been described in vitro and in animal model systems. Recent studies provide some evidence that this effect involves immune-mediated mechanisms. We investigated the influence of calcium-pterin on freshly isolated human peripheral blood mononuclear cells (PBMC) stimulated with the mitogens phytohaemagglutinin and concanavalin A in vitro. Influence of calcium-pterin on tryptophan-degrading enzyme indoleamine (2,3)-dioxygenase (IDO) and on neopterin production was monitored in supernatants of cells. Increased neopterin concentrations as well as accelerated tryptophan degradation have been found to predict poor prognosis in patients with cancer, and both these immunobiochemical pathways are induced by the pro-inflammatory cytokine interferon-gamma. Compared to unstimulated cells, mitogens induced degradation of tryptophan and formation of neopterin in PBMC, and upon addition of calcium-pterin, both biochemical results were suppressed in a dose-dependent way. Thus, calcium-pterin suppresses immunological pathways in vitro that in patients with malignant diseases characterize an unfavorable prognosis. The effect of the compound to suppress IDO activity could be of considerable relevance for the antitumoral effect of the compound because activation of the enzyme is considered as an immune-escape mechanism of tumor cells.
Winkler
Christiana
C
Division of Biological Chemistry, Biocentre, Innsbruck Medical University, Ludwig Boltzmann Institute of AIDS-Research, Innsbruck, Austria.
Schroecksnadel
Katharina
K
Moheno
Phillip
P
Meerbergen
Eric
E
Schennach
Harald
H
Fuchs
Dietmar
D
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology*; D002478:Cells, Cultured; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D008934:Mitogens / Q000037:antagonists & inhibitors / Q000494:pharmacology; D019798:Neopterin / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D011622:Pterins / Q000494:pharmacology*; D014364:Tryptophan / Q000097:blood*
D000970:Antineoplastic Agents; D008934:Mitogens; D011622:Pterins; D019798:Neopterin; D014364:Tryptophan; D002118:Calcium