Superoxide-dependent and -independent mitochondrial signaling during apoptosis in multiple myeloma cells.
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 (Deltapsi(m)). 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.
D000077584:2-Methoxyestradiol; D000111:Acetylcysteine; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D015938:Complement Membrane Attack Complex; D003165:Complement System Proteins; D003574:Cytochrome c Group / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D004351:Drug Resistance; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000378:metabolism*; D009101:Multiple Myeloma / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013481:Superoxides / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000975:Antioxidants; D015938:Complement Membrane Attack Complex; D003574:Cytochrome c Group; D006023:Glycoproteins; C047610:SC5b-9 protein complex; D013481:Superoxides; D004958:Estradiol; D000077584:2-Methoxyestradiol; D003907:Dexamethasone; D003165:Complement System Proteins; D000111:Acetylcysteine