Apoptosis and c-jun induction by cisplatin in a human melanoma cell line and a drug-resistant daughter cell line.
Cisplatin resistance was developed in the human melanoma cell line RPMI8322 by repeated short-term exposures to cisplatin. The most resistant daughter cell line, RPMI8322/CDDP-300, was 4-fold resistant to cisplatin, and partially cross-resistant to carboplatin, melphalan and UV, but not to BCNU. RPMI8322/CDDP-300 cells showed less apoptosis after cisplatin than the parental cells. The cisplatin resistance was not paralleled by a similar reduction in cellular cisplatin accumulation or DNA cross-links in RPMI8322/CDDP-300 cells, and these cells exhibited no increase in cellular glutathione or in mRNA encoding the DNA excision repair protein ERCC1 and XPB. Induction of c-jun mRNA by cisplatin was considerably lower in RPMI8322/CDDP-300 cells than in RPMI8322 cells, consistent with the possibility that c-jun induction may be involved in a pathway that triggers apoptosis after exposure to DNA damaging agents. However, c-jun induction is not necessary for apoptosis, since cisplatin also induced apoptosis in A14 rat embryo fibroblasts, cells in which the c-jun gene is deleted.
Zhao
R
R
Department of Oncology, Radiumhemmet, Karolinska Hospital, Stockholm, Sweden.
Rabo
Y B
YB
Egyházi
S
S
Andersson
A
A
Edgren
M R
MR
Linder
S
S
Hansson
J
J
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D002945:Cisplatin / Q000493:pharmacokinetics / Q000494:pharmacology*; D004249:DNA Damage / Q000187:drug effects; D004265:DNA Helicases; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005347:Fibroblasts / Q000166:cytology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D005978:Glutathione / Q000737:chemistry; D006801:Humans; D008545:Melanoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D009707:Nucleosomes / Q000235:genetics; D016755:Proto-Oncogene Proteins c-jun / Q000187:drug effects / Q000235:genetics*; D051381:Rats; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D009707:Nucleosomes; D016755:Proto-Oncogene Proteins c-jun; C072022:XPBC-ERCC-3 protein; D004265:DNA Helicases; D005978:Glutathione; D002945:Cisplatin