Abstract
Superoxide (O2−) radicals have been linked to apoptosis. Here, we show that 2-methoxyestradiol (2ME2)-induced apoptosis in multiple myeloma (MM) cells is associated with O2− generation, whereas dexamethasone (Dex)-induced apoptosis occurs without concurrent increase in O2−. In contrast, both these agents decrease mitochondrial transmembrane potential (Δψm). Treatment of MM cells with an antioxidant N-acetyl-L-cysteine blocks 2ME2, but not Dex-induced apoptosis as well as release of mitochondrial proteins cytochrome c (cyto c) and Smac. Taken together, these results demonstrate that there are at least two distinct apoptotic pathways: one dependent on O2−, which is induced by 2ME2 and is associated with release of cyto c and Smac; and the other an independent of O2−, which is triggered by Dex and associated with Smac release.
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Abbreviations
- MM:
-
multiple myeloma
- O2−:
-
superoxide
- cyto c:
-
cytochrome c
- Smac:
-
second mitochondrial activator of caspase
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Acknowledgements
This investigation was supported by NIH Grants 50947 and CA 78373, a Doris Duke Distinguished Clinical Research Scientist Award (KCA), The Myeloma Research Fund, and The Cure Myeloma Fund.
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Chauhan, D., Li, G., Sattler, M. et al. Superoxide-dependent and -independent mitochondrial signaling during apoptosis in multiple myeloma cells. Oncogene 22, 6296–6300 (2003). https://doi.org/10.1038/sj.onc.1206734
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DOI: https://doi.org/10.1038/sj.onc.1206734
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