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Journal of Cancer Research and Clinical Oncology

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01.02.2009 | Original Paper

Curcumin diminishes human osteoclastogenesis by inhibition of the signalosome-associated IκB kinase

verfasst von: Ivana von Metzler, Holger Krebbel, Ulrike Kuckelkorn, Ulrike Heider, Christian Jakob, Martin Kaiser, Claudia Fleissner, Evangelos Terpos, Orhan Sezer

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 2/2009

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Abstract

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 μM 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 IκB phosphorylation and NF-κB 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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Titel: Curcumin diminishes human osteoclastogenesis by inhibition of the signalosome-associated IκB kinase
verfasst von: Ivana von Metzler
Holger Krebbel
Ulrike Kuckelkorn
Ulrike Heider
Christian Jakob
Martin Kaiser
Claudia Fleissner
Evangelos Terpos
Orhan Sezer
Publikationsdatum: 01.02.2009
Verlag: Springer-Verlag
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 2/2009
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-008-0461-8

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