| Mitochondrial toxicity of the phyotochemicals daphnetoxin and daphnoretin--relevance for possible anti-cancer application. | |
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MedLine Citation:
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PMID: 19362137 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Daphnetoxin is a daphnane type orthoester diterpene found exclusively in plants of the family Thymelaeaceae while daphnoretin, a bis-coumarin derivative that is the major constituent of the bark of some plants of this family, can also be found in Leguminosae and Rutaceae. These two compounds are recognized to have different biological effects, including a possible anti-cancer activity. The subject of the present research was to compare their mitochondrial toxicity and also investigate a possible selectivity towards tumor cell lines. Wistar rat liver mitochondria and three distinct cell lines were used to investigate compound-induced toxicity. The results indicate that both test compounds are toxic to isolated mitochondrial fractions, especially when used at concentrations higher than 100 microM. However, daphnetoxin presented the highest toxicity including increased proton leak in the inner mitochondrial membrane, increased induction of the mitochondrial permeability transition pore, inhibition of ATP synthase and inhibition of the mitochondrial respiratory chain. Both compounds also inhibited cell proliferation, regardless of the cell line used. Up to the maximal concentration tested in cells, no mitochondrial effects were detected by vital epifluorescence imaging, indicating that inhibition of cell proliferation may also originate from mitochondrial-independent mechanisms. The results warrant careful assessment of toxicity vs. pharmacology benefits of both molecules. |
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Authors:
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Cátia V Diogo; Luís Félix; Sérgio Vilela; Ana Burgeiro; Inês A Barbosa; Maria J M Carvalho; Paulo J Oliveira; Francisco P Peixoto |
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Publication Detail:
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Type: Comparative Study; Journal Article Date: 2009-04-09 |
Journal Detail:
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Title: Toxicology in vitro : an international journal published in association with BIBRA Volume: 23 ISSN: 1879-3177 ISO Abbreviation: Toxicol In Vitro Publication Date: 2009 Aug |
Date Detail:
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Created Date: 2009-07-06 Completed Date: 2009-10-13 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8712158 Medline TA: Toxicol In Vitro Country: England |
Other Details:
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Languages: eng Pagination: 772-9 Citation Subset: IM |
Affiliation:
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Department of Zoology, Center for Neurosciences and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Line, Tumor Cell Proliferation / drug effects* Coumarins / administration & dosage, isolation & purification, toxicity* Daphne / chemistry Dose-Response Relationship, Drug Heterocyclic Compounds with 4 or More Rings / administration & dosage, isolation & purification, toxicity* Melanoma / metabolism Mice Microscopy, Fluorescence / methods Mitochondria, Liver / drug effects*, metabolism Mitochondrial Membrane Transport Proteins / drug effects, metabolism Mitochondrial Membranes / drug effects, metabolism Mitochondrial Proton-Translocating ATPases / antagonists & inhibitors Rats Rats, Wistar |
| Chemical | |
Reg. No./Substance:
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0/Coumarins; 0/Heterocyclic Compounds with 4 or More Rings; 0/Mitochondrial Membrane Transport Proteins; 0/mitochondrial permeability transition pore; 2034-69-7/daphnoretin; 28164-88-7/daphnetoxin; EC 3.6.3.-/Mitochondrial Proton-Translocating ATPases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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