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

doi:10.1159/000028185

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 journal › Article › peer-review

8 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 language	English (US)
Pages (from-to)	80-91
Number of pages	12
Journal	Pharmacology
Volume	56
Issue number	2
DOIs	https://doi.org/10.1159/000028185
State	Published - Feb 1998
Externally published	Yes

Keywords

5-Fluorouracil
Benzylacyclouridine
Prostate cancer
Uridine phosphorylase

ASJC Scopus subject areas

Pharmacology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1159/000028185

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@article{b1633327f8af4eac90c3e02cfe871e3b,

title = "Benzylacyclouridine enhances 5-fluorouracil cytotoxicity against human prostate cancer cell lines",

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.",

keywords = "5-Fluorouracil, Benzylacyclouridine, Prostate cancer, Uridine phosphorylase",

author = "Yee, {Lorrin K.} and Edward Chu and Pan, {Bai Chuan} and Chu, {Shih Hsi} and Chen, {Tian Min} and Lipsky, {Michael H.} and Chu, {Ming Y.W.} and Paul Calabresi",

year = "1998",

month = feb,

doi = "10.1159/000028185",

language = "English (US)",

volume = "56",

pages = "80--91",

journal = "Pharmacology",

issn = "0031-7012",

publisher = "S. Karger AG",

number = "2",

}

TY - JOUR

T1 - Benzylacyclouridine enhances 5-fluorouracil cytotoxicity against human prostate cancer cell lines

AU - Yee, Lorrin K.

AU - Chu, Edward

AU - Pan, Bai Chuan

AU - Chu, Shih Hsi

AU - Chen, Tian Min

AU - Lipsky, Michael H.

AU - Chu, Ming Y.W.

AU - Calabresi, Paul

PY - 1998/2

Y1 - 1998/2

N2 - 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.

AB - 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.

KW - 5-Fluorouracil

KW - Benzylacyclouridine

KW - Prostate cancer

KW - Uridine phosphorylase

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U2 - 10.1159/000028185

DO - 10.1159/000028185

M3 - Article

C2 - 9494066

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SN - 0031-7012

VL - 56

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EP - 91

JO - Pharmacology

JF - Pharmacology

IS - 2

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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