Deficient apoptotic process in cisplatin-resistant L1210 cells cannot account for the cellular response to various drug treatments

Biochemical and Biophysical Research Communications
Y CanitrotB Salles

Abstract

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.

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Citations

Apr 26, 2003·Journal of Toxicology and Environmental Health. Part a·T XiaoA Salahudeen
Nov 6, 2002·Nutrition and Cancer·Min LiJeanne Leung-Tack
Feb 9, 2000·Japanese Journal of Cancer Research : Gann·Y MinagawaN Terakawa
Mar 7, 2002·The Journal of Biological Chemistry·Odile HumbertDominique Lautier

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