Benzylacyclouridine enhances 5-fluorouracil cytotoxicity against human prostate cancer cell lines

Lorrin K. Yee, Edward Chu, Bai Chuan Pan, Shih Hsi Chu, Tian Min Chen, Michael H. Lipsky, Ming Y.W. Chu, Paul Calabresi

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

At a nontoxic growth inhibitory concentration benzyloxyacyclouridine (BAU), a potent and specific inhibitor of uridine phosphorylase (UrdPase), enhanced 5-fluorouracil (5-FU) cytotoxic activity against human prostate cancer PC-3 and DU-145 cell lines. The BAU/5-FU combination exhibited greater antitumor activity in vivo using PC-3 human xenografts compared to 5-FU alone, with no associated increase in animal host toxicity. The mechanism(s) responsible for the enhanced in vitro and in vivo activity of this combination may involve enhanced formation of the 5-FU nucleotide metabolites FdUMP, FdUTP, and FUTP resulting in enhanced inhibition of thymidylate synthase (TS) and increased incorporation of fluoropyrimidine metabolites into tumoral RNA and DNA.

Original languageEnglish (US)
Pages (from-to)80-91
Number of pages12
JournalPharmacology
Volume56
Issue number2
DOIs
StatePublished - Feb 1998
Externally publishedYes

Keywords

  • 5-Fluorouracil
  • Benzylacyclouridine
  • Prostate cancer
  • Uridine phosphorylase

ASJC Scopus subject areas

  • Pharmacology

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