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

AbstractPURPOSE:
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.
AuthorsXiao-Mei Hu, Toshihiko Hirano, Kitaro Oka
JournalCancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 51 Issue 2 Pg. 119-26 (Feb 2003) ISSN: 0344-5704 [Print] Germany
PMID12647012 (Publication Type: Journal Article)
Chemical References
  • Arsenicals
  • Oxides
  • P-Glycoprotein
  • arsenic trioxide
  • Daunorubicin
Topics
  • Apoptosis (drug effects)
  • Arsenicals (pharmacology)
  • Cell Division (drug effects)
  • Cell Survival (drug effects)
  • Daunorubicin (pharmacology)
  • Drug Resistance, Neoplasm
  • Humans
  • Oxides (pharmacology)
  • P-Glycoprotein (metabolism)
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma (pathology)
  • Tumor Cells, Cultured

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