Document Detail


Improved antitumoral properties of pure antiestrogen RU 58668-loaded liposomes in multiple myeloma.
MedLine Citation:
PMID:  16753295     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In most of multiple myeloma (MM) cells, the "pure" antiestrogen (AE) RU 58668 (RU) induced either a G1-arrest (LP-1, OPM-2, NCI-H929, U266 cells) or apoptosis (RPMI 8226 cells). In RPMI 8226 cells, RU activates a caspase-dependent cell death pathway leading to the release of cytochrome c, the decrease of the essential MM survival factor Mcl-1, the cleavage of Bid and the activation of caspases-3 and -8. Incorporation of RU in pegylated cholesterol-containing liposomes allowed a controlled RU release, improving its anti-proliferative and apoptotic effects in cells. In RPMI 8226 xenografts, i.v. injected RU-liposomes but not free RU, exhibited antitumor activity. In vivo, RU-liposomes triggered the mitochondrial death pathway, concomitantly with a down-regulation of Mcl-1 and Bid cleavage. The decrease of CD34 immunoreactivity indicated a reduction of angiogenesis. The decrease of VEGF secretion in vitro supported a direct effect of RU on angiogenesis. These pro-apoptotic and antiangiogenic effects were explained by a prolonged exposure to the drug and to the endocytosis capacity of liposomes which might increase RU uptake and bypass a membrane export of free RU. Thus, these combined enhanced activities of RU-liposomes support that such a delivery of an AE may constitute a strategy of benefit for MM treatment.
Authors:
Sébastien Maillard; Juliette Gauduchon; Véronique Marsaud; Fabrice Gouilleux; Elisabeth Connault; Paule Opolon; Elias Fattal; Brigitte Sola; Jack-Michel Renoir
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-06-05
Journal Detail:
Title:  The Journal of steroid biochemistry and molecular biology     Volume:  100     ISSN:  0960-0760     ISO Abbreviation:  J. Steroid Biochem. Mol. Biol.     Publication Date:  2006 Jul 
Date Detail:
Created Date:  2006-07-24     Completed Date:  2006-09-25     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  9015483     Medline TA:  J Steroid Biochem Mol Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  67-78     Citation Subset:  IM    
Affiliation:
CNRS UMR 8612, Université de Paris-Sud, Châtenay-Malabry, France.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antineoplastic Agents / isolation & purification,  pharmacology*
Apoptosis / drug effects
B-Lymphocytes / cytology,  drug effects
Cell Line, Tumor
Cell Proliferation / drug effects
Cells, Cultured
Delayed-Action Preparations
Drug Delivery Systems / methods
Estradiol / analogs & derivatives*,  isolation & purification,  pharmacology
Estrogen Antagonists / isolation & purification,  pharmacology*
Estrogen Receptor Modulators / administration & dosage,  pharmacology*
Female
Humans
Immunohistochemistry
Liposomes*
Mice
Mice, Nude
Models, Biological
Multiple Myeloma / drug therapy*,  pathology
Palatine Tonsil / cytology
Xenograft Model Antitumor Assays
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Delayed-Action Preparations; 0/Estrogen Antagonists; 0/Estrogen Receptor Modulators; 0/Liposomes; 151555-47-4/RU 58668; 50-28-2/Estradiol

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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