Abstract |
Interaction between 5-fluorouracil (5-FU) and FdUMP[10], a novel pro-drug formulation of the thymidylate synthase (TS) inhibitory nucleotide 5-fluoro-2'-deoxyuridine-5'-O-monophosphate ( FdUMP), was investigated to evaluate the feasibility of using these two forms of fluorinated pyrimidine in combination chemotherapy regimens. 5-FU and FdUMP[10] are expected to differ in their relative intracellular distribution of active metabolites, and their combined administration may result in either a positive or a negative interactive effect. The dose-response behaviors of 5-FU and FdUMP[10] toward H630 and H630-10 (human colorectal tumor) cells were first investigated separately. Effects on cell viability were measured using an assay for 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), while cytotoxicity and apoptosis were investigated using clonogenic and TUNEL assays, respectively. Exposure of H630 cells to concentrations of FdUMP[10] insufficient to inhibit cell proliferation as a single agent markedly increased the cytotoxicity of 5-FU. The results indicate that 5-FU and FdUMP[10] interact in a positive manner, and that combining these two forms of fluorinated pyrimidine may be clinically beneficial.
|
Authors | J Liu, J Kolath, J Anderson, C Kolar, T A Lawson, J Talmadge, W H Gmeiner |
Journal | Antisense & nucleic acid drug development
(Antisense Nucleic Acid Drug Dev)
Vol. 9
Issue 5
Pg. 481-6
(Oct 1999)
ISSN: 1087-2906 [Print] United States |
PMID | 10555156
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
|
Chemical References |
- Antimetabolites, Antineoplastic
- Prodrugs
- Fluorodeoxyuridylate
- Fluorouracil
|
Topics |
- Antimetabolites, Antineoplastic
(pharmacology)
- Cell Division
(drug effects)
- Colorectal Neoplasms
(pathology)
- Drug Synergism
- Fluorodeoxyuridylate
(pharmacology)
- Fluorouracil
(pharmacology)
- Humans
- Prodrugs
(pharmacology)
- Tumor Cells, Cultured
|