Potassium antimonyl tartrate induces reactive oxygen species-related apoptosis in human myeloid leukemic HL60 cells.
Potassium antimonyl tartrate (PAT), like arsenic trioxide (As2O3), has recently been shown to exert cytotoxicity towards acute promyelocytic leukemia (APL) cells. In the present study, we demonstrated that PAT treatment also inhibited cell growth of four acute myeloid leukemia (AML) cell lines, i.e., HL60, K562, KG1a and U937, that do not derive from APL. PAT, like As2O3, was further shown to induce apoptosis in HL60 cells as assessed by Hoechst 33342 staining and microscopical detection. Such an apoptotic process was associated with loss of mitochondrial potential and enhanced cellular production of reactive oxygen-related species; it was potentiated by co-treatment with buthionine sulfoximine, a pro-oxidant compound acting through inhibition of glutathione synthesis, and abolished in response to the antioxidant N-acetylcysteine, thus outlining that the toxicity of PAT, similarly to that of As2O3, is modulated by the cellular redox status. Pan-caspase inhibitors failed to inhibit PAT-triggered apoptosis of HL60 cells whereas they fully blocked that linked to As2O3, suggesting that PAT, unlike As2O3, does not require caspase activity for inducing apoptosis. PAT and As2O3 also differently affected intracellular pH, a key parameter commonly altered during apoptotic processes. Such data therefore indicate that PAT can exert cytotoxicity towards AML cells not deriving from APL such as HL60 cells, through inducing an apoptotic process which exhibits some similarities and some differences with that triggered by As2O3.
Lecureur
Valérie
V
Unité INSERM U456, Faculté de Pharmacie, Rennes Cedex, France.
Lagadic-Gossmann
Dominique
D
Fardel
Olivier
O
D000966:Antimony Potassium Tartrate / Q000494:pharmacology*; D017209:Apoptosis; D001151:Arsenic / Q000494:pharmacology; D020169:Caspases / Q000378:metabolism; D002455:Cell Division; D002470:Cell Survival; D005434:Flow Cytometry; D018922:HL-60 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D020128:Inhibitory Concentration 50; D020014:K562 Cells; D008564:Membrane Potentials; D008928:Mitochondria / Q000378:metabolism; D017382:Reactive Oxygen Species; D012556:Schistosomicides / Q000494:pharmacology*; D013997:Time Factors; D014407:Tumor Cells, Cultured; D020298:U937 Cells
D017382:Reactive Oxygen Species; D012556:Schistosomicides; D000966:Antimony Potassium Tartrate; D020169:Caspases; D001151:Arsenic