Abstract | PURPOSE: NAD(P)H:
quinone oxidoreductase (NQO(1)) catalyzes the two-electron reduction of quinones to hydroquinones. This reaction is believed to prevent the one-electron reduction of quinones that would result in redox cycling with generation of superoxide (O(2)(.-)). We have recently demonstrated that inhibition of NQO(1) with dicumarol increases intracellular O(2)(.-) production and inhibits the in vitro malignant phenotype of pancreatic cancer cells (J. Cullen et al., Cancer Res., 63: 5513-5520, 2003). We hypothesized that inhibition of NQO(1) would increase cell killing, induce oxidative stress, and inhibit in vivo tumor growth. EXPERIMENTAL DESIGN AND RESULTS: CONCLUSIONS:
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Authors | Anne Lewis, Matthew Ough, Ling Li, Marilyn M Hinkhouse, Justine M Ritchie, Douglas R Spitz, Joseph J Cullen |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research
(Clin Cancer Res)
Vol. 10
Issue 13
Pg. 4550-8
(Jul 01 2004)
ISSN: 1078-0432 [Print] United States |
PMID | 15240547
(Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Enzyme Inhibitors
- Hydroquinones
- Uncoupling Agents
- Vitamin K 3
- Dicumarol
- Cytochromes c
- NAD(P)H Dehydrogenase (Quinone)
- NQO1 protein, human
- NADPH - phenanthrenequinone oxidoreductase
- Quinone Reductases
- Poly(ADP-ribose) Polymerases
- Glutathione
- Oxygen
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Topics |
- Animals
- Apoptosis
- Blotting, Western
- Cell Line, Tumor
- Cell Survival
- Cytochromes c
(metabolism)
- Dicumarol
(pharmacology)
- Dose-Response Relationship, Drug
- Electrons
- Enzyme Inhibitors
(pharmacology)
- Flow Cytometry
- Glutathione
(metabolism)
- Humans
- Hydroquinones
(metabolism)
- Mice
- Mice, Nude
- NAD(P)H Dehydrogenase (Quinone)
(antagonists & inhibitors)
- Oxidative Stress
- Oxygen
(metabolism)
- Pancreatic Neoplasms
(drug therapy)
- Phenotype
- Poly(ADP-ribose) Polymerases
(metabolism)
- Quinone Reductases
(metabolism)
- Time Factors
- Uncoupling Agents
(pharmacology)
- Vitamin K 3
(metabolism)
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