Document Detail


Antifungal curcumin induces reactive oxygen species and triggers an early apoptosis but prevents hyphae development by targeting the global repressor TUP1 in Candida albicans.
MedLine Citation:
PMID:  20017731     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In the present study, we have investigated the antifungal effects of a natural polyphenol, CUR (curcumin), against albicans and non-albicans species of Candida and have shown its ability to inhibit the growth of all the tested strains. The inhibitory effects of CUR were independent of the status of the multidrug efflux pump proteins belonging to either ABC transporter (ATP-binding cassette transporter) or MFS (major facilitator) superfamilies of transporters. By using a systemic murine model of infection, we established that CUR and piperine, when administered together, caused a significant fungal load reduction (1.4log10) in kidneys of Swiss mice. Additionally, CUR raised the levels of ROS (reactive oxygen species), which, as revealed by annexin V-FITC labelling, triggered early apoptosis in Candida cells. Coincident with the raised ROS levels, mRNAs of tested oxidative stress-related genes [CAP1 (Candida albicans AP-1), CaIPF7817 (putative NADH-dependent flavin oxidoreductase), SOD2 (superoxide dismutase 2), GRP2 (NADPH-dependent methyl glyoxal reductase) and CAT1 (catalase 1)] were also elevated. The growth inhibitory effects of CUR could be reversed by the addition of natural and synthetic antioxidants. Notably, independent of ROS status, polyphenol CUR prevented hyphae development in both liquid and solid hypha-inducing media by targeting the global suppressor TUP1 (thymidine uptake 1). Taken together, our results provide the first evidence that CUR acts as an antifungal agent, via generation of oxidative stress, and inhibits hyphae development by targeting TUP1.
Authors:
Monika Sharma; Raman Manoharlal; Nidhi Puri; Rajendra Prasad
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Bioscience reports     Volume:  30     ISSN:  1573-4935     ISO Abbreviation:  Biosci. Rep.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-09-27     Completed Date:  2011-01-24     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8102797     Medline TA:  Biosci Rep     Country:  United States    
Other Details:
Languages:  eng     Pagination:  391-404     Citation Subset:  IM    
Affiliation:
Membrane Biology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi-110067, India. rp47jnu@gmail.com
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MeSH Terms
Descriptor/Qualifier:
Animals
Antifungal Agents / pharmacology*
Apoptosis / drug effects*
Candida / drug effects*,  genetics
Candida albicans / drug effects*,  genetics
Candidiasis / drug therapy,  microbiology
Curcumin / pharmacology*
Fungal Proteins / genetics,  metabolism
Humans
Hyphae / growth & development,  metabolism
Mice
Microbial Sensitivity Tests
Oxidative Stress / genetics
Reactive Oxygen Species / metabolism*
Repressor Proteins / genetics,  metabolism*
Chemical
Reg. No./Substance:
0/Antifungal Agents; 0/Fungal Proteins; 0/Reactive Oxygen Species; 0/Repressor Proteins; 458-37-7/Curcumin

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


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