Biomodulation of 5-Fu Cytotoxicity by Folinic Acid and Its Stereoisomers: in Vitro Experiments with Different Cell Lines of Prostatic Cancer

Overview

Journal Urol Res

Specialty Urology

Date 1995 Jan 1

PMID 7483142

Citations 1

Authors

J Breul

G Jakse

R Hartung

Affiliations

Soon will be listed here.

Abstract

The results of cytotoxic chemotherapy for advanced, hormone-escaped prostate cancer have been disappointing. Evaluation of the effect of new drugs or new combinations with already known ones is required. The antimetabolite 5-fluorouracil (5-FU) has been shown to be active in prostate cancer, acting via inhibition of thymidylate synthase, an essential enzyme in DNA de novo synthesis. Experiments with cell lines of different tumors have shown that 5-FU activity can be modulated by addition of the coenzyme tetrahydrofolic acid (folinic acid). We investigated the effect of folinic acid and its stereoisomers on 5-FU action in different cell lines of prostate cancer. It was found that addition of non-toxic folinic acid led to a two- to fourfold better antiproliferative effect of 5-FU. The unnatural 6R isomer, which is a compound of chemically synthesized folinic acid, inhibited the modulatory effect of the natural 6S isomer. Our results indicated that a combination of folinic acid and 5-FU may result in a better response of patients with hormone-resistant prostate cancer than of patients treated with 5-FU alone.

Citing Articles

Three-dimensional cultures of prostatic cells: tissue models for the development of novel anti-cancer therapies.

OConnor K Pharm Res. 1999; 16(4):486-93.

PMID: 10227701 DOI: 10.1023/a:1011906709680.

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