CPT-11-induced cell death in leukemic cells is not affected by the MDR phenotype

Abstract 

CPT-11 is a topoisomerase I (Topo I) inhibitor which was initially described as active in multi-drug resistance (MDR) tumors. The MDR phenomenon is characterized by the overexpression of efflux pumps which are able to extrude a range of drugs non-related chemical or functionally. In this work, we treated leukemic cells with CPT-11 300μM at 24h and compared its cytotoxicity with the activity of efflux pumps and with cell cycle phase. Our findings show that CPT-11 has a potent anti-tumor activity in leukemic cells regardless MDR phenotype and the cell cycle phase, suggesting new avenues to be explored in leukemia treatment.

Abbreviations:  ADR, adriamycin, ALL, acute lymphoid leukemia, AML, acute myeloid leukemia, ATP, adenosine triphosphate, cDNA, complementary desoxyribonucleic acid, CLL, chronic lymphoid leukemia, CML, chronic myeloid leukemia, CPT-11, 7-ethyl-10-[4-(1-poperidino)-1-piperidino]carbonoxyl camptothecin, CPTs, camptothecins, CSA, cyclosporin A, FAB, French–American–British, FBS, fetal bovine serum, FITC, fluorescein isotiocianate, IC₅₀, concentration able to inhibit 50% of cell growth, MDR, multi-drug resistance, MRP, multi-drug resistance-associated protein, MTT, 3-(4,5-di-methylazol-2-yl)-2,5-diphenyl tetrazolium bromide, P-gp, P-glycoprotein, PI, propidium iodide, Rho-123, rhodamine-123, RNAse, ribonuclease A, S.E.M., standard error of mean, Topo I, topoisomerase I, VCR, vincristine

Keywords:  Leukemia, CPT-11, Apoptosis, P-glycoprotein, Multi-drug resistance-associated protein