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Phenylarsine Oxide (PAO) More Intensely Induces Apoptosis in Acute Promyelocytic Leukemia and As2O3-Resistant APL Cell Lines than As2O3by Activating the Mitochondrial Pathway
- Source :
- Leukemia & Lymphoma. 45:987-995
- Publication Year :
- 2004
- Publisher :
- Informa UK Limited, 2004.
-
Abstract
- We studied the cytotoxic effect of an organic arsenical compound, phenylarsine oxide (PAO) on an acute promyelocytic leukemia (APL) cell line (NB4) and an As2O3-resistant NB4 subline (NB4/As). Cell growth was inhibited by 50% (IC50) upon 2-day treatment with As2O3 or PAO at 0.54 and 0.06 microM, respectively in NB4 cells (P = 0.025), and 2.80 and 0.08 microM, respectively in NB4/As (P = 0.030). 0.1 microM PAO increased the proportion of hypodiploid cells (50.3%) by a greater degree than the same dose of As2O3 (3.8%) in NB4 cells. In NB4 cells, 0.1 microM PAO reduced the mitochondrial transmembrane potential (20.5% in a PI(negative)-Rhodamine123(low) fraction) by a greater degree than 1 microM As2O3 (7.1%). Western blotting showed that 0.1 microM PAO downregulated the expression of both Bcl-2 and Bcl-X(L) proteins, whereas I microM As2O3 downregulated only Bcl-2 expression. These results suggest that the cytotoxic effect of PAO on an APL cell line and As2O3-resistant subline is significantly higher than that of As2O3. PAO-induced apoptosis seems to be related to the activation of the mitochondrial pathway and downregulation of both Bcl-2 and Bcl-X(L). PAO is a considerable agent for relapsed/refractory APL and for purging APL cells following stem cell transplantation.
- Subjects :
- Acute promyelocytic leukemia
Cancer Research
bcl-X Protein
Down-Regulation
Apoptosis
Biology
Arsenicals
Membrane Potentials
chemistry.chemical_compound
Arsenic Trioxide
Leukemia, Promyelocytic, Acute
Cell Line, Tumor
medicine
Humans
Cytotoxic T cell
Cyclin D1
Phenylarsine oxide
Cell Proliferation
Dose-Response Relationship, Drug
Cell growth
Oxides
Hematology
medicine.disease
Molecular biology
Mitochondria
Transplantation
Leukemia
Proto-Oncogene Proteins c-bcl-2
Oncology
chemistry
Biochemistry
Drug Resistance, Neoplasm
Cell culture
Subjects
Details
- ISSN :
- 10292403 and 10428194
- Volume :
- 45
- Database :
- OpenAIRE
- Journal :
- Leukemia & Lymphoma
- Accession number :
- edsair.doi.dedup.....43c249a5b627a6a9a6e49dfbb2fef0db