Susceptibility to lipid peroxidation of human hepatocellular carcinoma cell lines with different levels of multiple drug-resistant phenotype.
BACKGROUND
It has not been established whether the presence of intrinsic or acquired multiple drug-resistant (MDR) phenotype affects susceptibility to undergo iron-stimulated lipid peroxidation.


METHODS
To assess this point, human hepatocellular carcinoma cell lines with moderate, clinically relevant (P1) or elevated (P1(0.5)) MDR phenotype and their parental drug-sensitive (P5) cell line were exposed to ADP-Fe or ascorbate-Fe complexes and H2O2 in different experiments. Thiobarbituric acid-reactive substances (TBARS) were measured. Total cell glutathione, glutathione-S-transferase, total and selenium-dependent glutathione peroxidase activities, and cell alpha-tocopherol content were also determined.


RESULTS
P5 and P1 cell lines showed similar and significant formation of TBAR after 1-hour incubation exposure to iron complexes, whereas P1(0.5) subclone did not. No accumulation of TBAR was observed during the exposure to H2O2 in the three cell lines. Among antioxidants, only alpha-tocopherol cell content was significantly higher in P1(0.5) in comparison with either P1 or P5.


CONCLUSIONS
These data suggest that MDR phenotype development per se does not increase resistance to iron-related free radical attack in human hepatocellular carcinoma cell lines. Resistance to undergo lipid peroxidation is associated only to high degrees of drug resistance and appears more related to increased alpha-tocopherol cell content rather than an MDR phenotype.
Mazzanti
R
R
Istituto di Medicina Interna, Università di Firenze, Florence, Italy.
Fantappiè
O
O
Fabrizio
P
P
Relli
P
P
D000244:Adenosine Diphosphate / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000737:chemistry / Q000235:genetics / Q000473:pathology*; D018432:Drug Resistance, Multiple / Q000235:genetics / Q000502:physiology*; D005296:Ferrous Compounds / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D058085:Iron Compounds / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000502:physiology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D005296:Ferrous Compounds; D058085:Iron Compounds; C051140:iron(II)-ascorbic acid complex; D000244:Adenosine Diphosphate; D006861:Hydrogen Peroxide; D001205:Ascorbic Acid