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Redeployment-based drug screening identifies the anti-helminthic niclosamide as anti-myeloma therapy that also reduces free light chain production.
MedLine Citation:
PMID:  22829072     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Despite recent therapeutic advancements, multiple myeloma (MM) remains incurable and new therapies are needed, especially for the treatment of elderly and relapsed/refractory patients. We have screened a panel of 100 off-patent licensed oral drugs for anti-myeloma activity and identified niclosamide, an anti-helminthic. Niclosamide, at clinically achievable non-toxic concentrations, killed MM cell lines and primary MM cells as efficiently as or better than standard chemotherapy and existing anti-myeloma drugs individually or in combinations, with little impact on normal donor cells. Cell death was associated with markers of both apoptosis and autophagy. Importantly, niclosamide rapidly reduced free light chain (FLC) production by MM cell lines and primary MM. FLCs are a major cause of renal impairment in MM patients and light chain amyloid and FLC reduction is associated with reversal of tissue damage. Our data indicate that niclosamides anti-MM activity was mediated through the mitochondria with rapid loss of mitochondrial membrane potential, uncoupling of oxidative phosphorylation and production of mitochondrial superoxide. Niclosamide also modulated the nuclear factor-κB and STAT3 pathways in MM cells. In conclusion, our data indicate that MM cells can be selectively targeted using niclosamide while also reducing FLC secretion. Importantly, niclosamide is widely used at these concentrations with minimal toxicity.
Authors:
F L Khanim; B A M E Merrick; H V Giles; M Jankute; J B Jackson; L J Giles; J Birtwistle; C M Bunce; M T Drayson
Publication Detail:
Type:  Journal Article     Date:  2011-10-21
Journal Detail:
Title:  Blood cancer journal     Volume:  1     ISSN:  2044-5385     ISO Abbreviation:  Blood Cancer J     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2012-07-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101568469     Medline TA:  Blood Cancer J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e39     Citation Subset:  -    
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