Rotenone-Induced G2/M Cell Cycle Arrest and Apoptosis in a Human B Lymphoma Cell Line PW

Concentrations of rotenone (ROT) that block electron flow through mitochondrial complex I (100 nM) did not significantly alter either cell viability or the growth of PW cells. However, 10- to 50-fold higher concentrations (1–5 μM) were found to induce a dose-dependent cell cycle arrest predominantly...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2001-12, Vol.289 (5), p.973-978
Main Authors: Armstrong, Jeffrey S., Hornung, Brita, Lecane, Philip, Jones, Dean P., Knox, Susan J.
Format: Article
Language:English
Subjects:
Amino Acid Chloromethyl Ketones - pharmacology
apoptosis
Apoptosis - drug effects
B-Lymphocytes - cytology
B-Lymphocytes - drug effects
B-Lymphocytes - metabolism
Caspase Inhibitors
Cell Cycle - drug effects
Cell Division - drug effects
Cell Survival - drug effects
Cysteine Proteinase Inhibitors - pharmacology
Cytochrome c Group - metabolism
Electron Transport - drug effects
G2 Phase - drug effects
G2/M cell cycle arrest
Humans
Lymphoma, B-Cell - drug therapy
Lymphoma, B-Cell - metabolism
Lymphoma, B-Cell - pathology
mitochondria
Mitochondria - drug effects
Mitochondria - metabolism
Mitosis - drug effects
Reactive Oxygen Species - metabolism
rotenone
Rotenone - pharmacology
Tumor Cells, Cultured
Uncoupling Agents - pharmacology
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Summary:Concentrations of rotenone (ROT) that block electron flow through mitochondrial complex I (100 nM) did not significantly alter either cell viability or the growth of PW cells. However, 10- to 50-fold higher concentrations (1–5 μM) were found to induce a dose-dependent cell cycle arrest predominantly at the G2/M stage of the cycle and apoptosis. Apoptosis was dependent on the cell cycle arrest, since apoptosis but not the G2/M arrest was prevented with the broad spectrum caspase inhibitor zVADfmk. Biochemical features of apoptosis included mitochondrial cytochrome c release, reactive oxygen species generation, and the activation of procaspase 3. Thus, ROT inhibition of mitochondrial electron transport may be insufficient to induce apoptosis in PW cells. Instead, apoptosis in these cells occurs as a consequence of disruption of the cell cycle and is only indirectly dependent upon mitochondrial electron transport.
ISSN:0006-291X
1090-2104
DOI:10.1006/bbrc.2001.6054