Abstract |
The mechanism of apoptosis induced by treatment with As(2)O(3) alone or in combination with buthionine sulfoximine (BSO) was studied in NB4, U937, Namalwa, and Jurkat cells. As(2)O(3) at concentrations <2 micromol/L induced apoptosis in NB4 cells and Namalwa cells but not in U937 and Jurkat cells. As(2)O(3)-induced apoptosis in NB4 cells and Namalwa cells correlated with increase of H(2)O(2) and caspase activation without activation of c-Jun NH(2)-terminal kinase (JNK). BSO (10 micromol/L) depleted the reduced form of intracellular glutathione without inducing apoptosis but synergized with 1 micromol/L As(2)O(3) to induce apoptosis in all four cell lines. This synergy correlated with JNK activation. Treatment with As(2)O(3) plus BSO, but not with As(2)O(3) alone, increased the levels of death receptor (DR) 5 protein and caspase-8 cleavage. The JNK inhibitor SP600125 inhibited the increase in DR5 protein and attenuated apoptosis induced by treatment with As(2)O(3) plus BSO. These observations suggest that a DR-mediated pathway activated by JNK is involved in apoptosis induced by treatment with As(2)O(3) plus BSO.
|
Authors | Duo Chen, Rosemarie Chan, Samuel Waxman, Yongkui Jing |
Journal | Cancer research
(Cancer Res)
Vol. 66
Issue 23
Pg. 11416-23
(Dec 01 2006)
ISSN: 0008-5472 [Print] United States |
PMID | 17145888
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
|
Chemical References |
- Amino Acid Chloromethyl Ketones
- Anthracenes
- Arsenicals
- Caspase Inhibitors
- Oxides
- Receptors, TNF-Related Apoptosis-Inducing Ligand
- benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
- pyrazolanthrone
- Buthionine Sulfoximine
- Hydrogen Peroxide
- JNK Mitogen-Activated Protein Kinases
- Caspase 3
- Glutathione
- Arsenic Trioxide
|
Topics |
- Amino Acid Chloromethyl Ketones
(pharmacology)
- Anthracenes
(pharmacology)
- Apoptosis
(drug effects)
- Arsenic Trioxide
- Arsenicals
(pharmacology)
- Blotting, Western
- Buthionine Sulfoximine
(pharmacology)
- Caspase 3
(metabolism)
- Caspase Inhibitors
- Cell Proliferation
(drug effects)
- Dose-Response Relationship, Drug
- Drug Synergism
- Enzyme Activation
(drug effects)
- Glutathione
(metabolism)
- Humans
- Hydrogen Peroxide
(metabolism)
- JNK Mitogen-Activated Protein Kinases
(antagonists & inhibitors, metabolism)
- Jurkat Cells
- Leukemia
(metabolism, pathology)
- Lymphoma
(metabolism, pathology)
- Oxides
(pharmacology)
- Receptors, TNF-Related Apoptosis-Inducing Ligand
(metabolism)
- Time Factors
- U937 Cells
|