Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2003-2-13
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
13
pubmed:volume
22
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
906-18
pubmed:dateRevised
2006-11-15
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
pubmed:year
2003
pubmed:articleTitle
Inhibition of oxidative phosphorylation underlies the antiproliferative and proapoptotic effects of mofarotene (Ro 40-8757) in Burkitt's lymphoma cells.
pubmed:affiliation
Immunovirology and Biotherapy Unit, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't