Curcumin diminishes human osteoclastogenesis by inhibition of the signalosome-associated I[kappa]B kinase.
von Metzler, Ivana 1; Krebbel, Holger 1; Kuckelkorn, Ulrike 2; Heider, Ulrike 1; Jakob, Christian 1; Kaiser, Martin 1; Fleissner, Claudia 1; Terpos, Evangelos 3; Sezer, Orhan 1
[Article]
Journal of Cancer Research & Clinical Oncology.
135(2):173-179, February 2009.
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Purpose: Curcumin is a natural polyphenolic derogate extracted from spice turmeric, exhibiting anti-inflammatory and chemopreventive activities. It was described to interact with the signalosome-associated kinases and the proteasome-ubiquitin system, which both are involved in the osteoclastogenesis. Thus, we hypothesized that curcumin could diminish osteoclast differentiation and function.
Methods: For the experiments considering osteoclast differentiation and resorptional activities, preosteoclasts were cultured for 4 weeks and treated with curcumin at subapoptotic dosages. Derived mature osteoclasts were identified as large, multinucleated cells with expression of tartrate-resistant acid phosphatase activity. Formation of resorption lacunae, a hallmark of osteoclast activity, was quantified using dentine pits and light microscopy. The signaling pathways were examined by ELISA-based methods and by immunoblotting.
Results: Both 1 and 10 [mu]M curcumin abrogated osteoclast differentiation (by 56 and 81%) and function (by 56 and 99%) (P < 0.05) dose-dependently. The effects were accompanied by the inhibition of I[kappa]B phosphorylation and NF-[kappa]B activation. In contrast, subtoxic doses did not have any significant effects on proteasome inhibition.
Conclusion: This manuscript is the first report that describes the effects of curcumin toward human osteoclastogenesis, and builds the framework for clinical trials of curcumin in the treatment of cancer-induced lytic bone disease.
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