Diosgenin, a plant steroid, induces apoptosis in human rheumatoid arthritis synoviocytes with cyclooxygenase-2 overexpression.docVIP

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Diosgenin, a plant steroid, induces apoptosis in human rheumatoid arthritis synoviocytes with cyclooxygenase-2 overexpression.doc

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Diosgenin, a plant steroid, induces apoptosis in human rheumatoid arthritis synoviocytes with cyclooxygenase-2 overexpression

Available online /content/6/4/R373 Research article Open Access Vol 6 No 4 Diosgenin, a plant steroid, induces apoptosis in human rheumatoid arthritis synoviocytes with cyclooxygenase-2 overexpression Bertrand Liagre1, Pascale Vergne-Salle2, Cecile Corbiere1, Jean L Charissoux3 and Jean L Beneytout1 1Laboratoire de Biochimie, UPRES EA 1085, Faculté de Pharmacie, 2 rue du Docteur Marcland, 87025 Limoges Cedex, France 2Service de Rhumatologie, CHRU Dupuytren, 2 avenue Martin Luther King, 87042 Limoges Cedex, France 3Service dOrthopédie-Traumatologie, CHRU Dupuytren, 2 avenue Martin Luther King, 87042 Limoges Cedex, France Corresponding author: Bertrand Liagre, bertrand.liagre@unilim.fr Received: 19 Mar 2004 Revisions requested: 16 Apr 2004 Revisions received: 4 May 2004 Accepted: 18 May 2004 Published: 17 Jun 2004 Arthritis Res Ther 2004, 6:R373-R383 (DOI 10.1186/ar1199) /content/6/4/R373 ? 2004 Liagre et al.; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the articles original URL. Abstract In the present study, we have shown for the first time that a plant steroid, diosgenin, causes an inhibition of the growth of fibroblast-like synoviocytes from human rheumatoid arthritis, with apoptosis induction associated with cyclooxygenase-2 (COX-2) up-regulation. Celecoxib, a selective COX-2 inhibitor, provoked a large decrease in diosgenin-induced apoptosis even in the presence of exogenous prostaglandin E2, whereas interleukin-1β, a COX-2 inducer, strongly increased diosgenin- induced apoptosis of these synoviocytes. These findings suggest that the proapoptotic effect of diosgenin is associated with overexpression of COX-2 correlated with overproduction of endogenous prostaglandin E . We also observed a loss of 2 mitochondrial membrane potential, caspase-3