Source:http://linkedlifedata.com/resource/pubmed/id/12584570
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
6
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pubmed:dateCreated |
2003-2-13
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pubmed:abstractText |
In the search for retinoids active against Burkitt's lymphoma (BL), we found that the arotinoid mofarotene (Ro 40-8757) induced strong antiproliferative and apoptotic responses in most established BL cell lines as well as in primary BL cells. Ro 40-8757-induced apoptosis is associated with mitochondrial membrane depolarization, activation of caspase-3 and -9, and enhanced production of reactive oxygen species. These effects were related to a transient drop in intracellular ATP content, probably favored by a downregulation of NADH dehydrogenase subunit-1, a component of the mitochondrial respiratory chain (MRC) Complex I. Inhibition of MRC with thenoyltrifluoroacetone suppressed both the ATP recovery and apoptosis, confirming that the effects of Ro 40-8757 are mediated by changes in mitochondrial function. Compared to EBV-negative lines, EBV-carrying BLs were more resistant to Ro 40-8757-induced apoptosis. EBV infection and ectopic LMP-1 expression increased the resistance of BL cells to Ro 40-8757-induced apoptosis, probably through bcl-2 upregulation. Finally, we also show that 2-methoxyoestradiol, an inhibitor of the scavenger enzymes superoxide dismutases, enhanced Ro 40-8757-mediated apoptosis. These findings provide the rationale for evaluating the clinical efficacy of Ro 40-8757 in BL patients and suggest that the combination of Ro 40-8757 with inhibitors of scavenger enzymes may be a promising therapeutic approach for this aggressive lymphoma.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Triphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Antioxidants,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/Lactic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Morpholines,
http://linkedlifedata.com/resource/pubmed/chemical/NADH Dehydrogenase,
http://linkedlifedata.com/resource/pubmed/chemical/Reactive Oxygen Species,
http://linkedlifedata.com/resource/pubmed/chemical/Retinoids,
http://linkedlifedata.com/resource/pubmed/chemical/Superoxide Dismutase,
http://linkedlifedata.com/resource/pubmed/chemical/mofarotene
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0950-9232
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
13
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pubmed:volume |
22
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
906-18
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:12584570-Adenosine Triphosphate,
pubmed-meshheading:12584570-Antineoplastic Agents,
pubmed-meshheading:12584570-Antioxidants,
pubmed-meshheading:12584570-Apoptosis,
pubmed-meshheading:12584570-Burkitt Lymphoma,
pubmed-meshheading:12584570-Caspases,
pubmed-meshheading:12584570-Cell Division,
pubmed-meshheading:12584570-Cell Line,
pubmed-meshheading:12584570-Humans,
pubmed-meshheading:12584570-Lactic Acid,
pubmed-meshheading:12584570-Membrane Potentials,
pubmed-meshheading:12584570-Mitochondria,
pubmed-meshheading:12584570-Morpholines,
pubmed-meshheading:12584570-NADH Dehydrogenase,
pubmed-meshheading:12584570-Oxidative Phosphorylation,
pubmed-meshheading:12584570-Reactive Oxygen Species,
pubmed-meshheading:12584570-Retinoids,
pubmed-meshheading:12584570-Superoxide Dismutase
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pubmed:year |
2003
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pubmed:articleTitle |
Inhibition of oxidative phosphorylation underlies the antiproliferative and proapoptotic effects of mofarotene (Ro 40-8757) in Burkitt's lymphoma cells.
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pubmed:affiliation |
Immunovirology and Biotherapy Unit, Italy.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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