Abstract |
Since arsenic trioxide (As3+) has been successfully used in the treatment of acute promyelocytic leukemia (APL), its adverse effects on patients have been problematic and required a solution. Considering the good therapeutic potency and low toxicity of tetraarsenictetrasulfide (As4S4) in the treatment of APL, we investigated the effects of combining As4S4 and As3+ on the apoptosis and differentiation of NB4 and primary APL cells. As4S4, acting similarly to As3+, arrested the G1/S transition, induced the accumulation of cellular reactive oxygen species, and promoted apoptosis. Additionally, low concentrations of As4S4 (0.1-0.4 μM) induced differentiation of NB4 and primary APL cells. Compared with the As4S4- or As3+-treated groups, the combination of As4S4 and As3+ obviously promoted apoptosis and differentiation of NB4 and primary APL cells. Mechanistic studies suggested that As4S4 acted synergistically with As3+ to down-regulate Bcl-2 and nuclear factor-κB expression, up-regulate Bax and p53 expression, and induce activation of caspase-12 and caspase-3. Moreover, the combination of low concentrations of As4S4 and As3+ enhanced degradation of the promyelocytic leukemia- retinoic acid receptor α oncoprotein. In summary, As4S4 and As3+ synergistically induce the apoptosis and differentiation of NB4 and primary APL cells.
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Authors | Shuping Wang, Min Zhou, Jian Ouyang, Zhirong Geng, Zhilin Wang |
Journal | PloS one
(PLoS One)
Vol. 10
Issue 6
Pg. e0130343
( 2015)
ISSN: 1932-6203 [Electronic] United States |
PMID | 26110921
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Arsenicals
- Neoplasm Proteins
- Oxides
- Reactive Oxygen Species
- Sulfides
- Arsenic Trioxide
- tetraarsenic tetrasulfide
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Topics |
- Apoptosis
(drug effects)
- Arsenic Trioxide
- Arsenicals
(administration & dosage)
- Cell Differentiation
(drug effects)
- Drug Resistance, Neoplasm
- Drug Synergism
- Gene Expression Regulation, Neoplastic
(drug effects)
- Humans
- Leukemia, Promyelocytic, Acute
(drug therapy, genetics, pathology)
- Neoplasm Proteins
(biosynthesis, genetics)
- Oxides
(administration & dosage)
- Reactive Oxygen Species
(metabolism)
- Sulfides
(administration & dosage)
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