RRC ID 41818
Author Yen HC, Nien CY, Majima HJ, Lee CP, Chen SY, Wei JS, See LC.
Title Increase of lipid peroxidation by cisplatin in WI38 cells but not in SV40-transformed WI38 cells.
Journal J Biochem Mol Toxicol
Abstract Cisplatin (CPT) is an effective anticancer drug that causes cumulative toxicity to normal tissues. It has been suggested that CPT damages normal cells by causing oxidative stress, but it is not known whether it can induce similar oxidative damage to tumor cells. In this study, by using normal human lung fibroblast (W138) cells and SV40-transformed WI38 (VA13) cells as a model, we compared the effect of CPT on cytotoxicity, apoptosis, lipid peroxidation, and mitochondrial gene expression, which could be regulated by oxidative stress, between normal and tumor cells. CPT induced greater growth inhibition and percentage of apoptotic cells in VA13 cells. However, levels of esterified F(2)-isoprostanes and 4-hydroxy-2-nonenal, two specific products of lipid peroxidation, were increased by CPT in WI38 cells, but not in VA13 cells. Furthermore, the transcript level of mitochondrial 12S rRNA was augmented by CPT in both cells, but to a higher degree in WI38 cells. The data suggest a correlation between lipid peroxidation and cytotoxicity or increased mitochondrial transcript levels in WI38 cells but not in VA13 cells. The results also indicate an altered response of oxidative damage and mitochondrial gene regulation to CPT in the transformed phenotype of WI38 cells.
Volume 17(1)
Pages 39-46
Published 2003-1-1
DOI 10.1002/jbt.10059
PMID 12616645
MeSH Aldehydes / analysis Aldehydes / metabolism Apoptosis / drug effects Cell Division / drug effects Cell Line, Transformed Cell Transformation, Viral Chromatin / drug effects Chromatin / ultrastructure Cisplatin / pharmacology* DNA Fragmentation / drug effects F2-Isoprostanes / analysis F2-Isoprostanes / chemistry Fibroblasts / cytology Fibroblasts / drug effects Fibroblasts / metabolism* Fluorescent Antibody Technique Humans Lipid Peroxidation / drug effects* Mitochondria / metabolism Proteins / drug effects RNA, Ribosomal / metabolism Simian virus 40 Transcription, Genetic / drug effects
IF 3.606
Times Cited 11
Human and Animal Cells VA-13(RCB0251)