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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Marín-hernández, Alvaro Dong, Lan-feng Rodríguez-enríquez, Sara Akporiaye, Emmanuel T. Ralph, Stephen J. Moreno-sánchez, Rafael Hernández-esquivel, Luz Neuzil, Jiri |
| Description | Author Affiliation: Rodríguez-Enríquez S ( Departamento de Bioquímica, Instituto Nacional de Cardiología, Tlalpan, Mexico.) |
| Abstract | The effects of α-tocopheryl succinate (α-TOS), α-tocopheryl acetyl ether (α-TEA) and triphenylphosphonium-tagged vitamin E succinate (mitochondrially targeted vitamin E succinate; MitoVES) on energy-related mitochondrial functions were determined in mitochondria isolated from AS-30D hepatoma and rat liver, bovine heart sub-mitochondrial particles (SMPs), and in rodent and human carcinoma cell lines and rat hepatocytes. In isolated mitochondria, MitoVES stimulated basal respiration and ATP hydrolysis, but inhibited net state 3 (ADP-stimulated) respiration and Ca $^{2$ + uptake, by collapsing the membrane potential at low doses (1–10 μM). Uncoupled mitochondrial respiration and basal respiration of SMPs were inhibited by the three drugs at concentrations at least one order of magnitude higher and with different efficacy: MitoVES > α-TEA > α-TOS. At high doses (> 10 μM), the respiratory complex II (CII) was the most sensitive MitoVES target. Acting as an uncoupler at low doses, this agent stimulated total O $_{2}$ uptake, collapsed ∆ $ψ_{m}$ , inhibited oxidative phosphorylation and induced ATP depletion in rodent and human cancer cells more potently than in normal rat hepatocytes. These findings revealed that in situ tumor mitochondria are preferred targets of the drug, indicating its clinical relevance. |
| ISSN | 00063002 |
| Journal | Biochimica et Biophysica Acta (BBA) - Reviews on Cancer |
| Issue Number | 9 |
| Volume Number | 1817 |
| Language | English |
| Publisher | Elsevier |
| Publisher Date | 2012-09-01 |
| Publisher Place | Netherlands |
| Access Restriction | Open |
| Subject Keyword | Mitochondria Drug Effects Neoplasms Drug Therapy Vitamin E Analogs & Derivatives Adenosine Triphosphate Chemistry Animals Calcium Metabolism Cell Line, Tumor Cell Respiration Electron Transport Complex I Electron Transport Complex II Membrane Potential, Mitochondrial Physiology Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Biochemistry |
| Content Type | Text |
| Resource Type | Article |
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