Reference : Raloxifene-induced myeloma cell apoptosis: a study of nuclear factor-kappaB inhibition a...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
Human health sciences : Rheumatology
http://hdl.handle.net/2268/3675
Raloxifene-induced myeloma cell apoptosis: a study of nuclear factor-kappaB inhibition and gene expression signature.
English
Olivier, Sabine mailto [Université de Liège - ULg > Département de sciences fonctionnelles > Biochimie et biologie moléculaire >]
Close, Pierre mailto [Université de Liège - ULg > Département de pharmacie > Chimie médicale >]
Castermans, Emilie mailto [Université de Liège - ULg > Département des sciences cliniques > Département des sciences cliniques >]
de Leval, Laurence mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques - Département des sciences biomédicales et précliniques >]
Tabruyn, Sébastien mailto [Université de Liège - ULg > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire >]
Chariot, Alain mailto [Université de Liège - ULg > Département de pharmacie > Chimie médicale >]
Malaise, Michel mailto [Université de Liège - ULg > Département des sciences cliniques > Rhumatologie >]
Merville, Marie-Paule mailto [Université de Liège - ULg > Département de pharmacie > Chimie médicale >]
Bours, Vincent mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Génétique générale et humaine >]
Franchimont, Nathalie [> >]
May-2006
Molecular Pharmacology
American Society for Pharmacology and Experimental Therapeutics
69
5
1615-1623
Yes (verified by ORBi)
International
0026-895X
1521-0111
Bethesda
MD, USA
[en] NF kappa B ; multiple myeloma ; raloxifene
[en] Because multiple myeloma remains associated with a poor prognosis, novel drugs targeting specific signaling pathways are needed. The efficacy of selective estrogen receptor modulators for the treatment of multiple myeloma is not well documented. In the present report, we studied the antitumor activity of raloxifene, a selective estrogen receptor modulator, on multiple myeloma cell lines. Raloxifene effects were assessed by tetrazolium salt reduction assay, cell cycle analysis, and Western blotting. Mobility shift assay, immunoprecipitation, chromatin immunoprecipitation assay, and gene expression profiling were performed to characterize the mechanisms of raloxifene-induced activity. Indeed, raloxifene, as well as tamoxifen, decreased JJN-3 and U266 myeloma cell viability and induced caspase-dependent apoptosis. Raloxifene and tamoxifen also increased the cytotoxic response to vincristine and arsenic trioxide. Moreover, raloxifene inhibited constitutive nuclear factor-kappaB (NF-kappaB) activity in myeloma cells by removing p65 from its binding sites through estrogen receptor alpha interaction with p65. It is noteworthy that microarray analysis showed that raloxifene treatment decreased the expression of known NF-kappaB-regulated genes involved in myeloma cell survival and myeloma-induced bone lesions (e.g., c-myc, mip-1alpha, hgf, pac1,...) and induced the expression of a subset of genes regulating cellular cycle (e.g., p21, gadd34, cyclin G2,...). In conclusion, raloxifene induces myeloma cell cycle arrest and apoptosis partly through NF-kappaB-dependent mechanisms. These findings also provide a transcriptional profile of raloxifene treatment on multiple myeloma cells, offering the framework for future studies of selective estrogen receptor modulators therapy in multiple myeloma.
Giga-Signal Transduction
Fonds de la Recherche Scientifique (Communauté française de Belgique) - FNRS, TELEVIE, ARC ULG, FBC
Researchers ; Professionals ; Students
http://hdl.handle.net/2268/3675
also: http://hdl.handle.net/2268/19693 ; http://hdl.handle.net/2268/77746 ; http://hdl.handle.net/2268/77745
10.1124/mol.105.020479

File(s) associated to this reference

Fulltext file(s):

FileCommentaryVersionSizeAccess
Open access
PDF MOL PHARMACOL.pdfPublisher postprint570.66 kBView/Open

Bookmark and Share SFX Query

All documents in ORBi are protected by a user license.