title: Apoptosis in the absence of cytochrome c accumulation in the cytosol.
abstract: Cytochrome c release from mitochondria to and subsequent accumulation in the cytosol has been considered a prerequisite for apoptosis. In this study, we present evidence for apoptosis induction without accumulation of cytochrome c in the cytosol. U937 lymphoma cells treated with staurosprine released cytochrome c from mitochondria to cytosol prior to PARP cleavage and DNA fragmentation. However, U937 cells treated with BMD188 (a hydroxamic acid and a potent apoptosis inducer) did not demonstrate any cytochrome c accumulation in the cytosol during apoptosis induction. This different pattern of cytochrome c alterations was also observed with these two inducers on leukemic HL60 cells and epithelial PC3 cells. Furthermore, when PC3 cells were treated with a panel of apoptosis-inducing agents, it was found that camptothecin, bleomycin, VP16 and TNF-alpha induced varying amounts of cytosolic accumulation of cytochrome c either prior to or concurrent with PARP cleavage while vinblastine and BHPP did not. Taken together, the present results suggest that cytochrome c accumulation in the cytosol during apoptosis is a cell type- and inducer-dependent phenomenon.
authors.affiliation: Department of Radiation Oncology, Wayne State University, Detroit, Michigan 48202, USA. dtang@sum.science.wayne.edu
authors.forename: D G
authors.initials: DG
authors.lastname: Tang
authors.forename: L
authors.initials: L
authors.lastname: Li
authors.forename: Z
authors.initials: Z
authors.lastname: Zhu
authors.forename: B
authors.initials: B
authors.lastname: Joshi
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001710:Biotin / Q000031:analogs & derivatives / Q000494:pharmacology; D001761:Bleomycin / Q000494:pharmacology; D015153:Blotting, Western; D002166:Camptothecin / Q000494:pharmacology; D003574:Cytochrome c Group / Q000378:metabolism*; D003600:Cytosol / Q000737:chemistry / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005047:Etoposide / Q000494:pharmacology; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D008223:Lymphoma / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000378:metabolism; D010590:Phalloidine / Q000031:analogs & derivatives / Q000494:pharmacology; D011065:Poly(ADP-ribose) Polymerases / Q000032:analysis / Q000378:metabolism; D019311:Staurosporine / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014747:Vinblastine / Q000494:pharmacology
chemical_list: D000903:Antibiotics, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D003574:Cytochrome c Group; D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; D014409:Tumor Necrosis Factor-alpha; D001761:Bleomycin; C060047:4-(3-(biotinylaminohexamethylenaminocarbonyl)propanoylaminomethyl)-2-methyl-1,3-dithiolane-2-yl-(Ala(7))phalloidin; D010590:Phalloidine; D014747:Vinblastine; D005047:Etoposide; D001710:Biotin; D011065:Poly(ADP-ribose) Polymerases; D019311:Staurosporine; D002166:Camptothecin