Abstract |
Invasion of rat fibroblastic cells Rat-1 through Matrigel was shown to be promoted by transfection with tax gene of human T-cell leukemia virus type 1. We found that an oxidation-resistant type of vitamin C (Asc), Asc-2-O-phosphate (Asc2P), inhibited the invasion of the tax-transfected Rat-1 cells (W4 cells). Intracellular Asc (Ascin), after enzymatic dephosphorylation of administered Asc2P, was more abundant in W4 cells than in Rat-1 cells, and the ratio of dehydroascorbic acid versus Asc was increased in W4 cells but scarcely in Rat-1 cells, according to the enhanced level of intracellular reactive oxygen species ( ROSin) in W4 cells. Asc2P notably repressed the increases in both ROSin and secretion of matrix metalloproteases ( MMPs), but did not affect Tax protein expression in tax-transfectants. NF-kappa B activation, as evidenced by its translocation to the nucleus in W4 cells, was also repressed by Asc2P. Thus, the tax-promoted invasion together with the enhanced production of MMPs occurred with NF-kappa B activation and the increase in ROSin, both of which were effectively reduced by Asc2P. These findings indicate the therapeutic efficacy of Ascin-enriching agents for the prevention against tumor invasion in which ROSin plays a major role.
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Authors | N Nagao, T Etoh, S Yamaoka, T Okamoto, N Miwa |
Journal | Antioxidants & redox signaling
(Antioxid Redox Signal)
Vol. 2
Issue 4
Pg. 727-38
( 2000)
ISSN: 1523-0864 [Print] United States |
PMID | 11213478
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Gene Products, tax
- NF-kappa B
- ascorbate-2-phosphate
- Ascorbic Acid
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Topics |
- Animals
- Ascorbic Acid
(analogs & derivatives, pharmacology)
- Basement Membrane
(cytology)
- Cell Line
- Cell Movement
(genetics, physiology)
- Fibroblasts
(cytology, drug effects, metabolism)
- Gene Products, tax
(genetics)
- Genes, pX
- Humans
- NF-kappa B
(metabolism)
- Neoplasm Invasiveness
(genetics, physiopathology)
- Oxidative Stress
(drug effects)
- Phenotype
- Rats
- Transfection
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