| Sorafenib inhibits in vitro osteoclastogenesis by down-modulating Mcl-1. | |
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MedLine Citation:
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PMID: 23154882 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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The effect of the multi-kinase inhibitor Sorafenib was investigated in an in vitro model of human osteoclastogenesis, represented by peripheral blood mononuclear cells (PBMCs) induced to differentiate into osteoclast-like cells in presence of receptor activator of nuclear factor kappa B ligand (RANKL) plus macrophage-colony stimulating factor (M-CSF). Sorafenib significantly inhibited osteoclastic formation at clinically achievable concentrations (1-3 μM) and promoted autophagia with minimal induction of apoptosis. At the molecular levels, the M-CSF + RANKL combination increased the expression level of the Bcl-2 family member Mcl-1 protein, which is known to play a key role in the control of both cell survival and autophagia. The simultaneous treatment with Sorafenib significantly down-regulated endogenous Mcl-1 expression. Conversely, over-expression of Mcl-1 in primary human macrophages significantly counteracted the anti-osteoclastic activity of Sorafenib, strongly suggesting that Mcl-1 down-regulation played a major role in mediating the inhibitory activity of Sorafenib in cells of the osteoclastic lineage. |
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Authors:
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Erika Rimondi; Paola Secchiero; Elisabetta Melloni; Vittorio Grill; Giorgio Zauli |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-11-16 |
Journal Detail:
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Title: Investigational new drugs Volume: - ISSN: 1573-0646 ISO Abbreviation: Invest New Drugs Publication Date: 2012 Nov |
Date Detail:
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Created Date: 2012-11-16 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8309330 Medline TA: Invest New Drugs Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Life Sciences, University of Trieste, Trieste, Italy. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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