Document Detail


Curcumin inhibits growth of Saccharomyces cerevisiae through iron chelation.
MedLine Citation:
PMID:  21908599     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Curcumin, a polyphenol derived from turmeric, is an ancient therapeutic used in India for centuries to treat a wide array of ailments. Interest in curcumin has increased recently, with ongoing clinical trials exploring curcumin as an anticancer therapy and as a protectant against neurodegenerative diseases. In vitro, curcumin chelates metal ions. However, although diverse physiological effects have been documented for this compound, curcumin's mechanism of action on mammalian cells remains unclear. This study uses yeast as a model eukaryotic system to dissect the biological activity of curcumin. We found that yeast mutants lacking genes required for iron and copper homeostasis are hypersensitive to curcumin and that iron supplementation rescues this sensitivity. Curcumin penetrates yeast cells, concentrates in the endoplasmic reticulum (ER) membranes, and reduces the intracellular iron pool. Curcumin-treated, iron-starved cultures are enriched in unbudded cells, suggesting that the G(1) phase of the cell cycle is lengthened. A delay in cell cycle progression could, in part, explain the antitumorigenic properties associated with curcumin. We also demonstrate that curcumin causes a growth lag in cultured human cells that is remediated by the addition of exogenous iron. These findings suggest that curcumin-induced iron starvation is conserved from yeast to humans and underlies curcumin's medicinal properties.
Authors:
Steven Minear; Allyson F O'Donnell; Anna Ballew; Guri Giaever; Corey Nislow; Tim Stearns; Martha S Cyert
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-09-09
Journal Detail:
Title:  Eukaryotic cell     Volume:  10     ISSN:  1535-9786     ISO Abbreviation:  Eukaryotic Cell     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-11-02     Completed Date:  2012-05-01     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  101130731     Medline TA:  Eukaryot Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1574-81     Citation Subset:  IM    
Affiliation:
Department of Biology, Stanford University, Stanford, CA 94305-5020, USA.
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MeSH Terms
Descriptor/Qualifier:
Biological Transport
Cell Cycle / drug effects
Cell Cycle Checkpoints
Cell Line, Tumor
Cell Membrane / metabolism
Copper / metabolism
Curcumin / pharmacology*
Endoplasmic Reticulum / metabolism
Humans
Iron / analysis,  metabolism*
Iron Chelating Agents / pharmacology*
Mutation
Saccharomyces cerevisiae / drug effects*,  genetics,  growth & development,  metabolism
Grant Support
ID/Acronym/Agency:
81340//Canadian Institutes of Health Research; 84305//Canadian Institutes of Health Research; GM-48728/GM/NIGMS NIH HHS; GM52022/GM/NIGMS NIH HHS; R01 GM052022/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Iron Chelating Agents; 458-37-7/Curcumin; 7439-89-6/Iron; 7440-50-8/Copper
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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