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[Glutathione synthesis inhibitor enhances arsenic trioxide-induced apoptosis]
1Shanghai Institute of Hematology, Rui-Jin Hospital, Shanghai Second Medical University, Shanghai 200025.
Objective:
To illustrate the possible role of thiols (SH-groups) in arsenic trioxide (As2O3)-induced apoptosis.
Methods:
Leukemia (NB4, HL60, U937) and lymphoma (Jurkat and Namalwa) cell lines were treated with As2O3 together with buthionine sulfoximine (BSO), a selective inhibitor of gamma-glutamylcysteine synthetase. The mitochondrial transmembrane potentials (delta psi m) and the percentage of cells in apoptosis were measured by means of flow cytometry.
Results:
One mmol/L BSO significantly enhanced As2O3-induced delta psi m collapse and apoptosis in NB4 cells. One mumol/L As2O3 did not induce the delta psi m collapse and apoptosis in Namalwa, HL60, U937 and Jurkat cells, while these effects were induced significantly by the co-treatment of 1 mumol/L As2O3 and 1 mmol/L BSO.
Conclusion:
Thiols are important chemosensors of As2O3-induced delta psi m collapse and apoptosis.