Linked Life Data

20826775

Source:http://linkedlifedata.com/resource/pubmed/id/20826775

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
46
pubmed:dateCreated
2010-11-8
pubmed:abstractText
Prostate cancer is a major cause of mortality in men in developed countries. It has been reported that the naturally occurring antioxidant ?-tocopherol (vitamin E) attenuates prostate cancer cell proliferation in cultured cells and mouse models. We hypothesized that overexpression of the tocopherol transfer protein (TTP), a vitamin E-binding protein that regulates tocopherol status, will sensitize prostate cancer cells to the anti-proliferative actions of the vitamin. To test this notion, we manipulated the expression levels of TTP in cultured prostate cells (LNCaP, PC3, DU145, and RWPE-1) using overexpression and knockdown approaches. Treatment of cells with tocopherol caused a time- and dose-dependent inhibition of cell proliferation. Overexpression of TTP dramatically sensitized the cells to the apoptotic effects of ?-tocopherol, whereas reduction ("knockdown") of TTP expression resulted in resistance to the vitamin. TTP levels also augmented the inhibitory effects of vitamin E on proliferation in semi-solid medium. The sensitizing effects of TTP were paralleled by changes in the intracellular accumulation of a fluorescent analog of vitamin E and by a reduction in intracellular levels of reactive oxygen species and were not observed when a naturally occurring, ligand binding-defective mutant of TTP was used. We conclude that TTP sensitizes prostate cancer cells to the anti-proliferative effects of vitamin E and that this activity stems from the ability of protein to increase the intracellular accumulation of the antioxidant. These observations support the notion that individual changes in the expression level or activity of TTP may determine the responsiveness of prostate cancer patients to intervention strategies that utilize vitamin E.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1083-351X
pubmed:author
pubmed:issnType
Electronic
pubmed:day
12
pubmed:volume
285
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
35578-89
pubmed:dateRevised
2011-11-14
pubmed:meshHeading
pubmed-meshheading:20826775-Apoptosis, pubmed-meshheading:20826775-Blotting, Western, pubmed-meshheading:20826775-Carrier Proteins, pubmed-meshheading:20826775-Cell Line, Tumor, pubmed-meshheading:20826775-Cell Proliferation, pubmed-meshheading:20826775-Dose-Response Relationship, Drug, pubmed-meshheading:20826775-Drug Resistance, Neoplasm, pubmed-meshheading:20826775-HEK293 Cells, pubmed-meshheading:20826775-Hep G2 Cells, pubmed-meshheading:20826775-Humans, pubmed-meshheading:20826775-Male, pubmed-meshheading:20826775-Microscopy, Fluorescence, pubmed-meshheading:20826775-Mitochondria, pubmed-meshheading:20826775-Mutation, pubmed-meshheading:20826775-Poly(ADP-ribose) Polymerases, pubmed-meshheading:20826775-Prostatic Neoplasms, pubmed-meshheading:20826775-RNA Interference, pubmed-meshheading:20826775-Reactive Oxygen Species, pubmed-meshheading:20826775-Time Factors, pubmed-meshheading:20826775-Vitamin E, pubmed-meshheading:20826775-Vitamins, pubmed-meshheading:20826775-alpha-Tocopherol
pubmed:year
2010
pubmed:articleTitle
Tocopherol transfer protein sensitizes prostate cancer cells to vitamin E.
pubmed:affiliation
Department of Nutrition, Case Western Reserve University, Cleveland, Ohio 44106, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural