Document Detail


Vitamin E protects DNA from oxidative damage in human hepatocellular carcinoma cell lines.
MedLine Citation:
PMID:  15453640     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Ornella Fantappiè; Maura Lodovici; Paola Fabrizio; Serena Marchettia; Valentina Fabbroni; Michela Solazzo; Nadia Lasagna; Pietro Pantaleo; Roberto Mazzanti
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Free radical research     Volume:  38     ISSN:  1071-5762     ISO Abbreviation:  Free Radic. Res.     Publication Date:  2004 Jul 
Date Detail:
Created Date:  2004-09-29     Completed Date:  2005-01-24     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  9423872     Medline TA:  Free Radic Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  751-9     Citation Subset:  IM    
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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MeSH Terms
Descriptor/Qualifier:
Adenosine Diphosphate / analogs & derivatives*,  pharmacology
Carcinoma, Hepatocellular / genetics*,  metabolism,  pathology*
Cell Line, Tumor
DNA Damage / drug effects*,  radiation effects
Deoxyguanosine / analogs & derivatives*,  biosynthesis
Humans
Oxidative Stress / drug effects*,  physiology*,  radiation effects
Radiation, Ionizing
Thiobarbituric Acid Reactive Substances / metabolism
Tocopherols
Tumor Stem Cell Assay
Vitamin E / analogs & derivatives*,  metabolism,  pharmacology*
Chemical
Reg. No./Substance:
0/8-hydroxy-2'-deoxyguanosine; 0/Thiobarbituric Acid Reactive Substances; 0/adenosine diphosphate-ferric chelate; 1406-18-4/Vitamin E; 1406-66-2/Tocopherols; 58-64-0/Adenosine Diphosphate; 961-07-9/Deoxyguanosine

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