{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T00:25:56Z","timestamp":1792715156128,"version":"4.5.0"},"reference-count":33,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2012,2,22]],"date-time":"2012-02-22T00:00:00Z","timestamp":1329868800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2012,3]]},"abstract":"<jats:p><jats:bold>BACKGROUND AND PURPOSE<\/jats:bold> Hydrogen sulphide (H<jats:sub>2<\/jats:sub>S) and prostaglandins are both involved in inflammation, cancer and bone turnover, and non\u2010steroidal anti\u2010inflammatory drugs (NSAIDs) and H<jats:sub>2<\/jats:sub>S donors exhibit anti\u2010inflammatory and anti\u2010tumour properties. H<jats:sub>2<\/jats:sub>S\u2010releasing diclofenac (S\u2010DCF) derivatives are a novel class of NSAIDs combining the properties of a H<jats:sub>2<\/jats:sub>S donor with those of a conventional NSAID.<\/jats:p><jats:p><jats:bold>EXPERIMENTAL APPROACH<\/jats:bold> We studied the effects of the S\u2010DCF derivatives ACS15 and ACS32 on osteoclast and osteoblast differentiation and activity <jats:italic>in vitro<\/jats:italic>, human and mouse breast cancer cells support for osteoclast formation and signalling <jats:italic>in vitro<\/jats:italic>, and osteolysis <jats:italic>ex vivo<\/jats:italic>.<\/jats:p><jats:p><jats:bold>KEY RESULTS<\/jats:bold> The S\u2010diclofenac derivatives ACS15 and ACS32 inhibited the increase in osteoclast formation induced by human MDA\u2010MB\u2010231 and MCF\u20107 and mouse 4T1 breast cancer cells without affecting breast cancer cell viability. Conditioned media from human MDA\u2010MB\u2010231 cells enhanced I\u03baB phosphorylation and osteoclast formation and these effects were significantly inhibited following treatment by ACS15 and ACS32, whereas the parent compound diclofenac had no effects. ACS15 and ACS32 inhibited receptor activator of NF\u03baB ligand\u2010induced osteoclast formation and resorption, and caused caspase\u20103 activation and apoptosis in mature osteoclasts via a mechanism dependent on IKK\/NF\u03baB inhibition. In calvaria organ culture, human MDA\u2010MB\u2010231 cells caused osteolysis, and this effect was completely prevented following treatment with ACS15 and ACS32.<\/jats:p><jats:p><jats:bold>CONCLUSIONS AND IMPLICATIONS<\/jats:bold> S\u2010diclofenac derivatives inhibit osteoclast formation and activity, suppress breast cancer cell support for osteoclastogenesis and prevent osteolysis. This suggests that H<jats:sub>2<\/jats:sub>S\u2010releasing diclofenac derivatives exhibit anti\u2010resorptive properties, which might be of clinical value in the treatment of osteolytic bone disease.<\/jats:p>","DOI":"10.1111\/j.1476-5381.2011.01704.x","type":"journal-article","created":{"date-parts":[[2011,9,28]],"date-time":"2011-09-28T13:30:05Z","timestamp":1317216605000},"page":"1914-1925","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Hydrogen sulphide\u2010releasing diclofenac derivatives inhibit breast cancer\u2010induced osteoclastogenesis <i>in vitro<\/i> and prevent osteolysis <i>ex 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