Antitumor activity of brequinar sodium (Dup-785) against human head and neck squanmous cell carcinoma xenografts

B. J.M. Braakhuis, G. A.M.S. van Dongen, G. J. Peters, M. van Walsum, G. B. Snow

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

The effect of Brequinar sodium on the growth of xenografts established from head and neck squamous cell carcinomas (HNSCC) was assessed. Brequinar sodium is a novel drug, known to inhibit dihydroorotic acid dehydrogenase (DHO-DH), resulting in a decrease of the pyrimidine de novo synthesis. The drug was administered i.p. to tumor-bearing nude mice, once a day, during 5 days at a maximum tolerated dose of 50 mg/kg/day. Statistically significant growth delaying effects were observed in 4 out of 5 lines tested. In 3 of these lines the effect was moderate and short lasting, whereas in one line (HNX-LP) tumor growth rate was totally inhibited for a 17-day period. In this line, Brequinar sodium was superior to 5 drugs known to be active in HNSCC patients. In two tumor lines DHO-DH activity could be measured and the results are in agreement with the concept that there is a relation between Brequinar sodium sensitivity and enzyme activity.

Original languageEnglish
Pages (from-to)133-137
Number of pages5
JournalCancer Letters
Volume49
Issue number2
DOIs
Publication statusPublished - 1 Jan 1990

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