title: Dose-dependent effects of selenite (Se(4+)) on arsenite (As(3+))-induced apoptosis and differentiation in acute promyelocytic leukemia cells.
abstract: To enhance the therapeutic effects and decrease the adverse effects of arsenic on the treatment of acute promyelocytic leukemia, we investigated the co-effects of selenite (Se(4+)) and arsenite (As(3+)) on the apoptosis and differentiation of NB4 cells and primary APL cells. A 1.0-μM concentration of Se(4+) prevented the cells from undergoing As(3+)-induced apoptosis by inhibiting As(3+) uptake, eliminating As(3+)-generated reactive oxygen species, and repressing the mitochondria-mediated intrinsic apoptosis pathway. However, 4.0 μM Se(4+) exerted synergistic effects with As(3+) on cell apoptosis by promoting As(3+) uptake, downregulating nuclear factor-кB, and activating caspase-3. In addition to apoptosis, 1.0 and 3.2 μM Se(4+) showed contrasting effects on As(3+)-induced differentiation in NB4 cells and primary APL cells. The 3.2 μM Se(4+) enhanced As(3+)-induced differentiation by promoting the degradation of promyelocytic leukemia protein-retinoic acid receptor-α (PML-RARα) oncoprotein, but 1.0 μM Se(4+) did not have this effect. Based on mechanistic studies, Se(4+), which is similar to As(3+), might bind directly to Zn(2+)-binding sites of the PML RING domain, thus controlling the fate of PML-RARα oncoprotein.
authors.affiliation: State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing, China.
authors.forename: S
authors.initials: S
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Geng
authors.affiliation: State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing, China.
authors.forename: N
authors.initials: N
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing, China.
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.affiliation: State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Wang
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D018053:Arsenites / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism / Q000473:pathology*; D008954:Models, Biological; D015514:Oncogene Proteins, Fusion / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D020887:Selenious Acid / Q000494:pharmacology*
chemical_list: D018053:Arsenites; D015514:Oncogene Proteins, Fusion; D017382:Reactive Oxygen Species; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein; D020887:Selenious Acid; C015001:arsenite