Deficient apoptotic process in cisplatin-resistant L1210 cells cannot account for the cellular response to various drug treatments.
Apoptosis is a major determinant of the effectiveness of antitumor chemotherapy since most of the drugs used in cancer treatment provoke cell death by this process. We selected L1210/0.7R (7-fold) and L1210/3R (16-fold) murine leukemia cells resistant to cisplatin (CDDP) by adaptation of parental L1210/S cells to increasing drug concentration. L1210/0.7R exhibited a decreased apoptosis response to CDDP compared to parental L1210/S, while it was totally defective in L1210/3R as analyzed by cell morphology, DNA fragmentation, and poly(ADP-ribose) polymerase cleavage. This default in apoptosis did not result from differential expression of the antiapoptotic protein bcl-2 or from altered expression of p53. L1210/3R was resistant to other cross-linking agents and sensitive to topoisomerase II inhibitors and microtubule poisons. Whatever the drug sensitivity phenotype to these agents, L1210/3R was totally defective in apoptosis in response to drug treatment, showing that apoptosis control cannot be directly involved in the resistance process of these cell lines.
Canitrot
Y
Y
Institut de Pharmacologie et de Biologie Structurale, UPR CNRS 9062, Toulouse, France.
Frit
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P
Salles
B
B
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D019254:Genes, bcl-2; D016158:Genes, p53; D007939:Leukemia L1210 / Q000235:genetics / Q000473:pathology*; D051379:Mice; D010641:Phenotype
D000970:Antineoplastic Agents; D002945:Cisplatin