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- Title
Arsenic trioxide induces apoptosis equally in T lymphoblastoid leukemia MOLT-4 cells and P-gp-expressing daunorubicin-resistant MOLT-4 cells.
- Authors
Hu, Xiao-Mei; Hirano, Toshihiko; Oka, Kitaro
- Abstract
Purpose. To investigate the effects of arsenic trioxide (As2O3) on human T-lymphoblastoid leukemia MOLT-4 cells and P-gp-expressing daunorubicin-resistant MOLT-4 (MOLT-4/DNR) cells. Methods. Cell growth was measured by an MTT assay. Cell viability was determined by a dye exclusion test. The level of P-gp expression was estimated using phycoerythrin-conjugated anti-P-gp monoclonal antibody 17F9. The function of P-gp was evaluated in terms of rhodamine 123 (Rh123) efflux. The percentage of cells undergoing apoptosis was determined by flow cytometry after staining with annexin V-FITC and propidium iodide. Results. As2O3 inhibited the growth and survival of MOLT-4 and MOLT-4/DNR cells in a time- and dose-dependent manner. The 50% inhibitory concentrations of As2O3 (IC50) against the growth of these cell lines were 5.1 µmol/l and 5.0 µmol/l, respectively, when the cells were treated with As2O3 for 96 h. As2O3 induced an apoptotic morphology in both MOLT-4 and MOLT-4/DNR cell lines. These effects of As2O3 were time- and dose-dependent when the two cell lines were incubated in the presence of 1–8 µmol/l of As2O3 for 3–144 h. As2O3 treatment for 3 to 24 h at 5.0 µmol/l did not change the percentage of P-gp-expressing cells or the efflux ability of MOLT-4/DNR cells. Conclusion. As2O3 inhibited growth and induced apoptosis equally in MOLT-4 and MOLT-4/DNR cells, and this suppressive effect did not influence P-gp expression or function in MOLT-4/DNR cells.
- Subjects
CELL culture; APOPTOSIS; CELL death; NATIVE element minerals; MOLECULAR cloning; MONOCLONAL antibodies
- Publication
Cancer Chemotherapy & Pharmacology, 2003, Vol 51, Issue 2, p119
- ISSN
0344-5704
- Publication type
Article
- DOI
10.1007/s00280-002-0543-2