Diosgenin, a plant steroid, induces apoptosis in human rheumatoid arthritis synoviocytes with cyclooxygenase-2 overexpression.
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-1beta, 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 E2. We also observed a loss of mitochondrial membrane potential, caspase-3 activation, and DNA fragmentation after diosgenin treatment.
Liagre
Bertrand
B
Laboratoire de Biochimie, UPRES EA 1085, Faculté de Pharmacie, 2 rue du Docteur Marcland, 87025 Limoges Cedex, France. bertrand.liagre@unilim.fr
Vergne-Salle
Pascale
P
Corbiere
Cecile
C
Charissoux
Jean L
JL
Beneytout
Jean L
JL
D000368:Aged; D017209:Apoptosis / Q000187:drug effects*; D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D053938:DNA Fragmentation / Q000187:drug effects / Q000502:physiology; D015232:Dinoprostone / Q000096:biosynthesis / Q000378:metabolism; D004144:Diosgenin / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism / Q000502:physiology; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D007527:Isoenzymes / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects; D008565:Membrane Proteins; D008875:Middle Aged; D008928:Mitochondria / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology; D013583:Synovial Membrane / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D015854:Up-Regulation / Q000187:drug effects
D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D007527:Isoenzymes; D008565:Membrane Proteins; D010936:Plant Extracts; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D004144:Diosgenin; D015232:Dinoprostone