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Superoxide-dependent and -independent mitochondrial signaling during apoptosis in multiple myeloma cells

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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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Authors and Affiliations

  1. Department of Medical Oncology, The Jerome Lipper Multiple Myeloma Center, Dana Farber Cancer Institute, Harvard Medical School, Boston, 02115, MA, USA

    Dharminder Chauhan, Guilan Li, Martin Sattler, Klaus Podar, Constantine Mitsiades, Nicholas Mitsiades, Nikhil Munshi, Teru Hideshima & Kenneth C Anderson

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  1. Dharminder Chauhan
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  2. Guilan Li
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  3. Martin Sattler
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  7. Nikhil Munshi
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  8. Teru Hideshima
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  9. Kenneth C Anderson
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Correspondence to Kenneth C Anderson.

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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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