Source:http://linkedlifedata.com/resource/pubmed/id/15453640
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
7
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pubmed:dateCreated |
2004-9-29
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pubmed:abstractText |
Expression of multiple drug resistant (MDR) phenotype and over-expression of P-glycoprotein (P-gp) in the human hepatocellular carcinoma (HCC) cell clone P1(0.5), derived from the PLC/PRF/5 cell line (P5), are associated with strong resistance to oxidative stress and a significant (p < 0.01) increase in intracellular vitamin E content as compared with the parental cell line. This study evaluates the role of vitamin E in conferring resistance to drugs and oxidative stress in P1(0.5) cells. Parental drug-sensitive cells, P5, were incubated in alpha-tocopherol succinate (alpha-TS, 5 microM for 24 h) enriched medium to increase intracellular vitamin E content to levels comparable to those observed in P1(0.5) cells at basal conditions. Susceptibility to lipid peroxidation and oxidative DNA damage were assessed by measuring the concentration of thiobarbituric-reactive substances (TBARS) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) at basal and after experimental conditions. Cell capacity to form colonies and resistance to doxorubicin were also studied. P5 cells, treated with alpha-TS, became resistant to ADP-Fe3+ and to ionizing radiation-induced lipid peroxidation as P1(0.5) cells. Exposure to ADP-Fe3+ or ionizing radiation increased TBARS and the 8-OHdG content in the P5 cells, while vitamin E enrichment abolished these effects. Irradiation doses at 5 cGy increased TBARS and 8-OHdG. They also inhibited cell capacity to form colonies in the untreated P5 cells. Incubation with alpha-TS fully reverted this effect and significantly (p < 0.01) reduced the inhibitory effect of cell proliferation induced by irradiation doses at >500 cGy. Resistance to doxorubicin was not affected by alpha-TS. These observations demonstrate the role of vitamin E in conferring protection from lipid peroxidation, ionizing radiation and oxidative DNA damage on the human HCC cell line. They also rule out any role of P-gp over-expression as being responsible for these observations in cells with MDR phenotype expression.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/8-hydroxy-2'-deoxyguanosine,
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Diphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Deoxyguanosine,
http://linkedlifedata.com/resource/pubmed/chemical/Thiobarbituric Acid Reactive...,
http://linkedlifedata.com/resource/pubmed/chemical/Tocopherols,
http://linkedlifedata.com/resource/pubmed/chemical/Vitamin E,
http://linkedlifedata.com/resource/pubmed/chemical/adenosine diphosphate-ferric chelate
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
1071-5762
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
38
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
751-9
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:15453640-Adenosine Diphosphate,
pubmed-meshheading:15453640-Carcinoma, Hepatocellular,
pubmed-meshheading:15453640-Cell Line, Tumor,
pubmed-meshheading:15453640-DNA Damage,
pubmed-meshheading:15453640-Deoxyguanosine,
pubmed-meshheading:15453640-Humans,
pubmed-meshheading:15453640-Oxidative Stress,
pubmed-meshheading:15453640-Radiation, Ionizing,
pubmed-meshheading:15453640-Thiobarbituric Acid Reactive Substances,
pubmed-meshheading:15453640-Tocopherols,
pubmed-meshheading:15453640-Tumor Stem Cell Assay,
pubmed-meshheading:15453640-Vitamin E
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pubmed:year |
2004
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pubmed:articleTitle |
Vitamin E protects DNA from oxidative damage in human hepatocellular carcinoma cell lines.
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pubmed:affiliation |
Department of Internal Medicine, U.A. Oncologia, Azienda Ospedaliero-Universitaria Careggi, Viale G.B. Morgagni 85, I-50134 Florence, Italy.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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