Arsenic trioxide induces apoptosis equally in T lymphoblastoid leukemia MOLT-4 cells and P-gp-expressing daunorubicin-resistant MOLT-4 cells.
OBJECTIVE
To investigate the effects of arsenic trioxide (As(2)O(3)) 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
As(2)O(3) 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 As(2)O(3) (IC(50)) against the growth of these cell lines were 5.1 micromol/l and 5.0 micromol/l, respectively, when the cells were treated with As(2)O(3) for 96 h. As(2)O(3) induced an apoptotic morphology in both MOLT-4 and MOLT-4/DNR cell lines. These effects of As(2)O(3) were time- and dose-dependent when the two cell lines were incubated in the presence of 1-8 micromol/l of As(2)O(3) for 3-144 h. As(2)O(3) treatment for 3 to 24 h at 5.0 micromol/l did not change the percentage of P-gp-expressing cells or the efflux ability of MOLT-4/DNR cells.


CONCLUSIONS
As(2)O(3) 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.
Hu
Xiao-Mei
XM
Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
Hirano
Toshihiko
T
Oka
Kitaro
K
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003630:Daunorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D006801:Humans; D010087:Oxides / Q000494:pharmacology*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000473:pathology*; D014407:Tumor Cells, Cultured
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D001152:Arsenicals; D010087:Oxides; D000077237:Arsenic Trioxide; D003630:Daunorubicin