Diamide and cyclosporin A enhanced arsenic trioxide-induced apoptosis in NB4 cells.
- Author:
Yun YU
1
;
Peimin JIA
;
Ying HUANG
;
Xun CAI
;
Guoqiang CHEN
Author Information
- Publication Type:Journal Article
- MeSH: Antineoplastic Agents; pharmacology; therapeutic use; Apoptosis; Arsenicals; pharmacology; therapeutic use; Cyclosporine; pharmacology; Diamide; pharmacology; Drug Synergism; Enzyme Inhibitors; pharmacology; Humans; Leukemia, Promyelocytic, Acute; drug therapy; pathology; Membrane Potentials; drug effects; physiology; Mitochondria; physiology; Oxides; pharmacology; therapeutic use; Sulfhydryl Reagents; pharmacology; Tumor Cells, Cultured
- From: Chinese Journal of Hematology 2002;23(5):254-257
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo 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.
METHODSNB4 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.
RESULTSBoth 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.
CONCLUSIONSAs(2)O(3)-induced DeltaPsim disruption possibly involves with thiol oxidation or crosslink of important components especially ANT-related molecules.
