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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
2011-5-10
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pubmed:abstractText |
Mitochondria play central roles in cell life as a source of energy and in cell death by inducing apoptosis. Many important functions of mitochondria change in cancer, and these organelles can be a target of chemotherapy. The widely used anticancer drug doxorubicin (DOX) causes cell death, inhibition of cell cycle/proliferation and mitochondrial impairment. However, the mechanism of such impairment is not completely understood. In our study we used confocal and two-photon fluorescence imaging together with enzymatic and respirometric analysis to study short- and long-term effects of doxorubicin on mitochondria in various human carcinoma cells. We show that short-term (<30 min) effects include i) rapid changes in mitochondrial redox potentials towards a more oxidized state (flavoproteins and NADH), ii) mitochondrial depolarization, iii) elevated matrix calcium levels, and iv) mitochondrial ROS production, demonstrating a complex pattern of mitochondrial alterations. Significant inhibition of mitochondrial endogenous and uncoupled respiration, ATP depletion and changes in the activities of marker enzymes were observed after 48 h of DOX treatment (long-term effects) associated with cell cycle arrest and death.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0006-3002
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pubmed:author |
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pubmed:copyrightInfo |
Copyright © 2011 Elsevier B.V. All rights reserved.
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pubmed:issnType |
Print
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pubmed:volume |
1813
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1144-52
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pubmed:meshHeading |
pubmed-meshheading:21406203-Adenosine Triphosphate,
pubmed-meshheading:21406203-Antibiotics, Antineoplastic,
pubmed-meshheading:21406203-Apoptosis,
pubmed-meshheading:21406203-Calcium,
pubmed-meshheading:21406203-Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone,
pubmed-meshheading:21406203-Cell Cycle,
pubmed-meshheading:21406203-Cell Line, Tumor,
pubmed-meshheading:21406203-Cell Respiration,
pubmed-meshheading:21406203-Cell Survival,
pubmed-meshheading:21406203-Citrate (si)-Synthase,
pubmed-meshheading:21406203-Dose-Response Relationship, Drug,
pubmed-meshheading:21406203-Doxorubicin,
pubmed-meshheading:21406203-Electron Transport Complex I,
pubmed-meshheading:21406203-HT29 Cells,
pubmed-meshheading:21406203-Humans,
pubmed-meshheading:21406203-Membrane Potential, Mitochondrial,
pubmed-meshheading:21406203-Microscopy, Confocal,
pubmed-meshheading:21406203-Mitochondria,
pubmed-meshheading:21406203-Oxidation-Reduction,
pubmed-meshheading:21406203-Reactive Oxygen Species,
pubmed-meshheading:21406203-Time Factors,
pubmed-meshheading:21406203-Uncoupling Agents
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pubmed:year |
2011
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pubmed:articleTitle |
Changes in mitochondrial redox state, membrane potential and calcium precede mitochondrial dysfunction in doxorubicin-induced cell death.
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pubmed:affiliation |
Department of Heart Surgery, Innsbruck Medical University, Innrain 66, Innsbruck A-6020, Austria. andrey.kuznetsov@uki.at
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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