Please use this identifier to cite or link to this item:
https://hdl.handle.net/10316/12630
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Moreira, Paula I. | - |
dc.contributor.author | Custódio, José | - |
dc.contributor.author | Moreno, António | - |
dc.contributor.author | Oliveira, Catarina R. | - |
dc.contributor.author | Santos, Maria S. | - |
dc.date.accessioned | 2010-03-01T13:53:35Z | - |
dc.date.available | 2010-03-01T13:53:35Z | - |
dc.date.issued | 2006-04-14 | - |
dc.identifier.citation | The Journal of Biological Chemistry. 281:15 (2006) 10143-10152 | en_US |
dc.identifier.issn | 0021-9258 | - |
dc.identifier.uri | https://hdl.handle.net/10316/12630 | - |
dc.description.abstract | This study evaluated the action of tamoxifen and estradiol on the function of isolated liver mitochondria. We observed that although tamoxifen and estradiol per se did not affect mitochondrial complexes II, III, or IV, complex I is affected, this effect being more drastic (except for state 4 of respiration) when mitochondria were coincubated with both drugs. Furthermore, using two respiratory chain inhibitors, rotenone and diphenyliodonium chloride, we identified the flavin mononucleotide site of complex I as the target of tamoxifen and/or estradiol action(s). Tamoxifen (25 microm) per se induced a significant increase in hydrogen peroxide production and state 4 of respiration. Additionally, a significant decrease in respiratory control ratio, transmembrane, and depolarization potentials were observed. Estradiol per se decreased carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP)-stimulated respiration, state 3 of respiration, and respiratory control ratio and increased lag phase of repolarization. With the exception of state 4 of respiration whose increase induced by tamoxifen was reversed by the presence of estradiol, the effects of tamoxifen were highly exacerbated when estradiol was present. We observed that 10 microm tamoxifen in the presence of estradiol affected mitochondria significantly by decreasing FCCP-stimulated respiration, state 3 of respiration, respiratory control ratio, and ADP depolarization and increasing the lag phase of repolarization. All of the deleterious effects induced by 25 microm tamoxifen were highly exacerbated in the presence of estradiol. Furthermore, we observed that the effects of both compounds were independent of estrogen receptors because the pure estrogen antagonist ICI 182,780 did not interfere with tamoxifen and/or estradiol detrimental effects. Altogether, our data provide a mechanistic explanation for the multiple cytotoxic effects of tamoxifen including its capacity to destroy tamoxifen-resistant breast cancer cells in the presence of estradiol. This new piece of information provides a basis for the development of new and promising anticancer therapeutic strategies | en_US |
dc.language.iso | eng | en_US |
dc.publisher | The American Society for Biochemistry and Molecular Biology | en_US |
dc.rights | openAccess | en_US |
dc.title | Tamoxifen and estradiol interact with the flavin mononucleotide site of complex I leading to mitochondrial failure | en_US |
dc.type | article | en_US |
dc.identifier.doi | 10.1074/jbc.M510249200 | - |
uc.controloAutoridade | Sim | - |
item.fulltext | Com Texto completo | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.cerifentitytype | Publications | - |
item.grantfulltext | open | - |
item.languageiso639-1 | en | - |
item.openairetype | article | - |
crisitem.author.dept | Faculty of Sciences and Technology | - |
crisitem.author.parentdept | University of Coimbra | - |
crisitem.author.researchunit | CNC - Center for Neuroscience and Cell Biology | - |
crisitem.author.researchunit | MARE - Marine and Environmental Sciences Centre | - |
crisitem.author.researchunit | CNC - Center for Neuroscience and Cell Biology | - |
crisitem.author.researchunit | CNC - Center for Neuroscience and Cell Biology | - |
crisitem.author.orcid | 0000-0001-5177-6747 | - |
crisitem.author.orcid | 0000-0003-3575-7604 | - |
crisitem.author.orcid | 0000-0001-6942-4328 | - |
crisitem.author.orcid | 0000-0002-6881-9392 | - |
Appears in Collections: | FFUC- Artigos em Revistas Internacionais FMUC Medicina - Artigos em Revistas Internacionais FCTUC Ciências da Vida - Artigos em Revistas Internacionais |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
Tamoxifen and estradiol interact.pdf | 925.17 kB | Adobe PDF | View/Open |
SCOPUSTM
Citations
111
checked on Sep 23, 2024
WEB OF SCIENCETM
Citations
105
checked on Sep 2, 2024
Page view(s)
386
checked on Sep 24, 2024
Download(s) 20
1,066
checked on Sep 24, 2024
Google ScholarTM
Check
Altmetric
Altmetric
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.