Document Detail


Antiproliferative effects of cannabinoid agonists on deep infiltrating endometriosis.
MedLine Citation:
PMID:  21057002     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Deep infiltrating endometriosis (DIE) is characterized by chronic pain, hyperproliferation of endometriotic cells and fibrosis. Since cannabinoids are endowed with antiproliferative and antifibrotic properties, in addition to their psychogenic and analgesic effects, cannabinoid agonists have been evaluated in DIE both in vitro and in vivo. The in vitro effects of the cannabinoid agonist WIN 55212-2 were evaluated on primary endometriotic and endometrial stromal and epithelial cell lines extracted from patients with or without DIE. Cell proliferation was determined by thymidine incorporation and production of reactive oxygen species by spectrofluorometry. ERK and Akt pathways were studied by immunoblotting. Immunoblotting of α-smooth muscle actin was studied as evidence of myofibroblastic transformation. The in vivo effects of WIN 55212-2 were evaluated on Nude mice implanted with human deep infiltrating endometriotic nodules. The in vitro treatment of stromal endometriotic cells by WIN 55212-2 decreased cell proliferation, reactive oxygen species production, and α-smooth muscle actin expression. The decrease in cell proliferation induced by WIN 55212-2 was not associated with a decrease in ERK activation, but was associated with the inhibition of Akt activation. WIN 55212-2 abrogated the growth of endometriotic tissue implanted in Nude mice. Cannabinoid agonists exert anti-proliferative effects on stromal endometriotic cells linked to the inhibition of the Akt pathway. These beneficial effects of cannabinoid agonists on DIE have been confirmed in vivo.
Authors:
Mahaut Leconte; Carole Nicco; Charlotte Ngô; Sylviane Arkwright; Christiane Chéreau; Jean Guibourdenche; Bernard Weill; Charles Chapron; Bertrand Dousset; Frédéric Batteux
Publication Detail:
Type:  Evaluation Studies; Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-11-05
Journal Detail:
Title:  The American journal of pathology     Volume:  177     ISSN:  1525-2191     ISO Abbreviation:  Am. J. Pathol.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-12-01     Completed Date:  2011-03-15     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  0370502     Medline TA:  Am J Pathol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2963-70     Citation Subset:  AIM; IM    
Affiliation:
Laboratoire d'immunologie, Université Paris Descartes, Paris, France.
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MeSH Terms
Descriptor/Qualifier:
Animals
Benzoxazines / adverse effects,  pharmacology
Cannabinoid Receptor Agonists*
Cannabinoids / adverse effects,  pharmacology*,  therapeutic use
Cell Culture Techniques
Cell Proliferation / drug effects*
Cells, Cultured
Endometriosis / drug therapy,  metabolism,  pathology*
Female
Humans
Hydrogen Peroxide / metabolism
Mice
Mice, Nude
Morpholines / adverse effects,  pharmacology
Naphthalenes / adverse effects,  pharmacology
Reactive Oxygen Species / metabolism
Receptors, Cannabinoid / metabolism
Rectal Diseases / drug therapy,  metabolism,  pathology*
Transplantation, Heterologous
Chemical
Reg. No./Substance:
0/Benzoxazines; 0/Cannabinoid Receptor Agonists; 0/Cannabinoids; 0/Morpholines; 0/Naphthalenes; 0/Reactive Oxygen Species; 0/Receptors, Cannabinoid; 134959-51-6/Win 55212-2; 7722-84-1/Hydrogen Peroxide
Comments/Corrections

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