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Receptor activator of nuclear factor\u2010kappaB (NF\u2010\u03baB) ligand (RANKL), a member of the tumor necrosis factor superfamily, has been implicated as a major mediator of bone resorption, suggesting that agents that can suppress RANKL signaling might inhibit osteoclastogenesis, a process closely linked to bone resorption. We therefore investigated whether butein, a tetrahydroxychalcone, could inhibit RANKL signaling and suppress osteoclastogenesis induced by RANKL or tumor cells. We found that human multiple myeloma cells (MM.1S and U266), breast tumor cells (MDA\u2010MB\u2010231) and prostate tumor cells (PC\u20103) induced differentiation of macrophages to osteoclasts, as indicated by tartrate\u2010resistant acid phosphatase (TRAP)\u2010positive cells, and that butein suppressed this process. The chalcone also suppressed the expression of RANKL by the tumor cells. We further found that butein suppressed RANKL\u2010induced NF\u2010\u03baB activation and that this suppression correlated with the inhibition of I\u03baB\u03b1 kinase and suppression of phosphorylation and degradation of I\u03baB\u03b1, an inhibitor of NF\u2010\u03baB. Finally, butein also suppressed the RANKL\u2010induced differentiation of macrophages to osteoclasts in a dose\u2010dependent and time\u2010dependent manner. Collectively, our results indicate that butein suppresses the osteoclastogenesis induced by tumor cells and by RANKL, by suppression of the NF\u2010\u03baB activation pathway.<\/jats:p>","DOI":"10.1002\/ijc.25868","type":"journal-article","created":{"date-parts":[[2010,12,17]],"date-time":"2010-12-17T16:19:45Z","timestamp":1292602785000},"page":"2062-2072","source":"Crossref","is-referenced-by-count":27,"title":["Butein, a tetrahydroxychalcone, suppresses cancer\u2010induced osteoclastogenesis through inhibition of receptor activator of nuclear factor\u2010kappaB ligand 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