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The IMP dehydrogenase inhibitor mycophenolic acid antagonizes the CTP synthetase inhibitor 3-deazauridine in MOLT-3 human leukemia cells: a central role for phosphoribosyl pyrophosphate

By A. A. van Berg, P. A. Mooyer, H. van Lenthe, E. H. Stet, R. A. de Abreu, A. B. van Kuilenburg and A. H. van Gennip

Abstract

Mycophenolic acid, an inhibitor of the enzyme IMP dehydrogenase, antagonizes the CTP synthetase inhibitor 3-deazauridine in its anti-proliferative effects on MOLT-3 human T leukemia cells. No depletion of CTP occurred, and decreased amounts of 3-deazuridine-triphosphate were measured in cells incubated with mycophenolic acid and 3-deazuridine. Most probably, these phenomena are related to the increased amounts of PRPP observed, which can result in an increased pyrimidine biosynthesis de novo and, as a consequence, a decreased metabolism of 3-deazauridine via the salvage pathwa

Year: 1995
DOI identifier: 10.1016/0006-2952(95)00228-r
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Provided by: NARCIS
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