Increase of lipid peroxidation by cisplatin in WI38 cells but not in SV40-transformed WI38 cells.
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.
Yen
Hsiu-Chuan
HC
School of Medical Technology, Chang Gung University, Kwei-Shan, Tao-Yuan 333, Taiwan, Republic of China.
Nien
Chung-Yi
CY
Majima
Hideyuki J
HJ
Lee
Chia-Pei
CP
Chen
Sz-Yun
SY
Wei
Jeng-Shu
JS
See
Lai-Chu
LC
D000447:Aldehydes / Q000032:analysis / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D002843:Chromatin / Q000187:drug effects / Q000648:ultrastructure; D002945:Cisplatin / Q000494:pharmacology*; D053938:DNA Fragmentation / Q000187:drug effects; D028441:F2-Isoprostanes / Q000032:analysis / Q000737:chemistry; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects*; D008928:Mitochondria / Q000378:metabolism; D011506:Proteins / Q000187:drug effects; D012335:RNA, Ribosomal / Q000378:metabolism; D013539:Simian virus 40; D014158:Transcription, Genetic / Q000187:drug effects
D000447:Aldehydes; D002843:Chromatin; D028441:F2-Isoprostanes; D011506:Proteins; D012335:RNA, Ribosomal; C027576:4-hydroxy-2-nonenal; D002945:Cisplatin