Arsenic trioxide induces apoptosis equally in T lymphoblastoid leukemia MOLT-4 cells and P-gp-expressing daunorubicin-resistant MOLT-4 cells.

Article Details

Citation

Copy to clipboard

Hu XM, Hirano T, Oka K

Arsenic trioxide induces apoptosis equally in T lymphoblastoid leukemia MOLT-4 cells and P-gp-expressing daunorubicin-resistant MOLT-4 cells.

Cancer Chemother Pharmacol. 2003 Feb;51(2):119-26. Epub 2002 Nov 20.

PubMed ID

12647012 [ View in PubMed

]

Abstract

PURPOSE: 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. CONCLUSION: 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.

DrugBank Data that Cites this Article

Drug Transporters

Drug	Transporter	Kind	Organism	Pharmacological Action	Actions
Arsenic trioxide	P-glycoprotein 1	Protein	Humans	Unknown	Inhibitor	Details