[Diamide and cyclosporin A enhanced arsenic trioxide-induced apoptosis in NB4 cells].
OBJECTIVE
To investigate the effects of mitochondrial membrane permeability transition pore (MPT)-opened agent diamide and MPT-closed agent cyclosporin A on arsenic trioxide (As(2)O(3))-induced apoptosis in acute promyelocytic leukemia (APL) cell line NB4.


METHODS
NB4 cells were treated with As(2)O(3) alone or in combination with diamide or cyclosporin A in different concentrations. Cell apoptosis was assessed by the morphological observation, Annexin-V assay, distribution of cellular DNA contents and genomic DNA electrophoresis. The mitochondrial transmembrane potentials (DeltaPsim) were detected by flow cytometry according to the intensity of rhodamine 123 uptake in cells.


RESULTS
Both diamide and cyclosporin A significantly enhanced As(2)O(3)-induced apoptosis in NB4 cells. The DeltaPsim collapse induced by As(2)O(3) was also enforced by combined treatment with diamide or cyclospo-rin A. 1 micromol/L As(2)O(3) alone treatment for 72 hours led to DeltaPsim disruption in 27.9% of cells, while combined treatment of As(2)O(3) and diamide or cyclosporin A increased DeltaPsim disruption cells to 59.7% and 42.2%, respectively.


CONCLUSIONS
As(2)O(3)-induced DeltaPsim disruption possibly involves with thiol oxidation or crosslink of important components especially ANT-related molecules.
Shanghai Institute of Hematology, Rui-Jin Hospital, Shanghai Second Medical University, Shanghai 200025, China.
Yun
Y
Yu
Peimin
P
Jia
Ying
Y
Huang
Xun
X
Cai
Guoqiang
G
Chen
D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology* / Q000627:therapeutic use; D016572:Cyclosporine / Q000494:pharmacology*; D003958:Diamide / Q000494:pharmacology*; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy / Q000473:pathology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008928:Mitochondria / Q000502:physiology*; D010087:Oxides / Q000494:pharmacology* / Q000627:therapeutic use; D013439:Sulfhydryl Reagents / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D001152:Arsenicals; D004791:Enzyme Inhibitors; D010087:Oxides; D013439:Sulfhydryl Reagents; D003958:Diamide; D016572:Cyclosporine; D000077237:Arsenic Trioxide