{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T08:14:21Z","timestamp":1791447261216,"version":"4.3.3"},"reference-count":44,"publisher":"Portland Press Ltd.","issue":"6","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2010,12,1]]},"abstract":"<jats:p>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\u2013FITC 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.<\/jats:p>","DOI":"10.1042\/bsr20090151","type":"journal-article","created":{"date-parts":[[2009,12,23]],"date-time":"2009-12-23T11:17:28Z","timestamp":1261567048000},"page":"391-404","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":136,"title":["Antifungal curcumin induces reactive oxygen species and triggers an early apoptosis but prevents hyphae development by targeting the global repressor\n                    <i>TUP1<\/i>\n                    in\n                    <i>Candida albicans<\/i>"],"prefix":"10.1042","volume":"30","author":[{"given":"Monika","family":"Sharma","sequence":"first","affiliation":[{"name":"Membrane Biology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi-110067, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raman","family":"Manoharlal","sequence":"additional","affiliation":[{"name":"Membrane Biology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi-110067, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nidhi","family":"Puri","sequence":"additional","affiliation":[{"name":"Membrane Biology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi-110067, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajendra","family":"Prasad","sequence":"additional","affiliation":[{"name":"Membrane Biology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi-110067, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2010,9,24]]},"reference":[{"key":"2021111618094879100_B1","volume-title":"Candida and Candidosis: A Review and Bibliography","author":"Odds","year":"1988"},{"key":"2021111618094879100_B2","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1128\/CMR.11.2.382","article-title":"Clinical, cellular, and molecular factors that contribute to antifungal drug resistance","volume":"11","author":"White","year":"1998","journal-title":"Clin. Microbiol. Rev."},{"key":"2021111618094879100_B3"},{"key":"2021111618094879100_B4","doi-asserted-by":"crossref","first-page":"3747","DOI":"10.1128\/AAC.00929-07","article-title":"The Ssk1p response regulator and Chk1p histidine kinase mutants of Candida albicans are hypersensitive to fluconazole and voriconazole","volume":"51","author":"Chauhan","year":"2007","journal-title":"Antimicrob. Agents Chemother."},{"key":"2021111618094879100_B5","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1111\/j.1567-1364.2008.00394.x","article-title":"Iron deprivation induces EFG1-mediated hyphal development in Candida albicans without affecting biofilm formation","volume":"8","author":"Hameed","year":"2008","journal-title":"FEMS Yeast Res."},{"key":"2021111618094879100_B6","doi-asserted-by":"crossref","first-page":"1704","DOI":"10.1128\/AAC.46.6.1704-1713.2002","article-title":"Resistance mechanisms in clinical isolates of Candida albicans","volume":"46","author":"White","year":"2002","journal-title":"Antimicrob. Agents Chemother."},{"key":"2021111618094879100_B7","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1021\/mp700113r","article-title":"Bioavailability of curcumin: problems and promises","volume":"4","author":"Anand","year":"2007","journal-title":"Mol. Pharm."},{"key":"2021111618094879100_B8","doi-asserted-by":"crossref","first-page":"1839","DOI":"10.1073\/pnas.90.5.1839","article-title":"Three inhibitors of type\u00a01 human immunodeficiency virus long terminal repeat-directed gene expression and virus replication","volume":"90","author":"Li","year":"1993","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2021111618094879100_B9","doi-asserted-by":"crossref","first-page":"25284","DOI":"10.1074\/jbc.M414645200","article-title":"Thioredoxin reductase is irreversibly modified by curcumin: a novel molecular mechanism for its anticancer activity","volume":"280","author":"Fang","year":"2005","journal-title":"J. Biol. Chem."},{"key":"2021111618094879100_B10","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1158\/1535-7163.1101.3.9","article-title":"Effect of curcumin on normal and tumor cells: role of glutathione and Bcl-2","volume":"3","author":"Syng-Ai","year":"2004","journal-title":"Mol. Cancer Ther."},{"key":"2021111618094879100_B11","doi-asserted-by":"crossref","first-page":"2234","DOI":"10.1248\/bpb.31.2234","article-title":"In vitro synergism of fluconazole and baicalein against clinical isolates of Candida albicans resistant to fluconazole","volume":"31","author":"Huang","year":"2008","journal-title":"Biol. Pharm. Bull."},{"key":"2021111618094879100_B12","doi-asserted-by":"crossref","first-page":"3113","DOI":"10.1128\/AAC.46.10.3113-3117.2002","article-title":"Endogenous reactive oxygen species is an important mediator of miconazole antifungal effect","volume":"46","author":"Kobayashi","year":"2002","journal-title":"Antimicrob. Agents Chemother."},{"key":"2021111618094879100_B13","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1099\/mic.0.26578-0","article-title":"Aspirin commits yeast cells to apoptosis depending on carbon source","volume":"150","author":"Balzan","year":"2004","journal-title":"Microbiology"},{"key":"2021111618094879100_B14","doi-asserted-by":"crossref","first-page":"14327","DOI":"10.1073\/pnas.2332326100","article-title":"Apoptosis induced by environmental stresses and amphotericin B in Candida albicans","volume":"100","author":"Phillips","year":"2003","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2021111618094879100_B15","doi-asserted-by":"crossref","first-page":"3442","DOI":"10.1128\/AAC.49.8.3442-3452.2005","article-title":"Functional analysis of CaIPT1, a sphingolipid biosynthetic gene involved in multidrug resistance and morphogenesis of Candida albicans","volume":"49","author":"Prasad","year":"2005","journal-title":"Antimicrob. Agents Chemother."},{"key":"2021111618094879100_B16","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1055\/s-2006-957450","article-title":"Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers","volume":"64","author":"Shoba","year":"1998","journal-title":"Planta Med."},{"key":"2021111618094879100_B17","doi-asserted-by":"crossref","first-page":"e40","DOI":"10.1111\/j.1440-1681.2009.05187.x","article-title":"Ascorbic acid decreases the antifungal effect of fluconazole in the treatment of candidiasis","volume":"36","author":"Wang","year":"2009","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"2021111618094879100_B18","doi-asserted-by":"crossref","first-page":"2300","DOI":"10.1128\/AAC.40.10.2300","article-title":"Susceptibilities of Candida albicans multidrug transporter mutants to various antifungal agents and other metabolic inhibitors","volume":"40","author":"Sanglard","year":"1996","journal-title":"Antimicrob. Agents Chemother."},{"key":"2021111618094879100_B19","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1099\/00221287-143-2-405","article-title":"Cloning of Candida albicans genes conferring resistance to azole antifungal agents: characterization of CDR2, a new multidrug ABC transporter gene","volume":"143","author":"Sanglard","year":"1997","journal-title":"Microbiology"},{"key":"2021111618094879100_B20","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1046\/j.1365-2958.2000.01899.x","article-title":"Targeted gene disruption in Candida albicans wild-type strains: the role of the MDR1 gene in fluconazole resistance of clinical Candida albicans isolates","volume":"36","author":"Wirshing","year":"2000","journal-title":"Mol. Microbiol."},{"key":"2021111618094879100_B21","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1046\/j.1439-0507.1999.00498.x","article-title":"Molecular aspects of fluconazole resistance development in Candida albicans","volume":"42","author":"Franz","year":"1999","journal-title":"Mycoses"},{"key":"2021111618094879100_B22","doi-asserted-by":"crossref","first-page":"3065","DOI":"10.1128\/AAC.42.12.3065","article-title":"Multiple molecular mechanisms contribute to a stepwise development of fluconazole resistance in clinical Candida albicans strains","volume":"42","author":"Franz","year":"1998","journal-title":"Antimicrob. Agents Chemother."},{"key":"2021111618094879100_B23","doi-asserted-by":"crossref","first-page":"4753","DOI":"10.1093\/emboj\/20.17.4753","article-title":"NRG1, a repressor of filamentous growth in C. albicans, is downregulated during filament induction","volume":"20","author":"Braun","year":"2001","journal-title":"EMBO J."},{"key":"2021111618094879100_B24","doi-asserted-by":"crossref","first-page":"1982","DOI":"10.1093\/emboj\/16.8.1982","article-title":"Efg1p, an essential regulator of morphogenesis of the human pathogen Candida albicans, is a member of a conserved class of bHLH proteins regulating morphogenetic processes in fungi","volume":"16","author":"Stoldt","year":"1997","journal-title":"EMBO J."},{"key":"2021111618094879100_B25","doi-asserted-by":"crossref","first-page":"6339","DOI":"10.1128\/JB.181.20.6339-6346.1999","article-title":"Ras signaling is required for serum-induced hyphal differentiation in Candida albicans","volume":"181","author":"Feng","year":"1999","journal-title":"J. Bacteriol."},{"key":"2021111618094879100_B26","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1128\/IAI.68.2.518-525.2000","article-title":"Defective hyphal development and avirulence caused by a deletion of the SSK1 response regulator gene in Candida albicans","volume":"68","author":"Calera","year":"2000","journal-title":"Infect. Immun."},{"key":"2021111618094879100_B27","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.bbrc.2007.05.081","article-title":"CaIPF7817 is involved in the regulation of redox homeostasis in Candida albicans","volume":"359","author":"Jia","year":"2007","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2021111618094879100_B28","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1128\/JB.181.3.700-708.1999","article-title":"The bZip transcription factor Cap1p is involved in multidrug resistance and oxidative stress response in Candida albicans","volume":"181","author":"Alarco","year":"1999","journal-title":"J. Bacteriol."},{"key":"2021111618094879100_B29","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1016\/j.freeradbiomed.2005.11.019","article-title":"Cap1p is involved in multiple pathways of oxidative stress response in Candida albicans","volume":"40","author":"Wang","year":"2006","journal-title":"Free Radical Biol. Med."},{"key":"2021111618094879100_B30","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1128\/EC.3.6.1639-1652.2004","article-title":"TAC1, transcriptional activator of CDR genes, is a new transcription factor involved in the regulation of Candida albicans ABC transporters CDR1 and CDR2","volume":"3","author":"Coste","year":"2004","journal-title":"Eukaryot. Cell"},{"key":"2021111618094879100_B31","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1126\/science.288.5468.1062","article-title":"A high-affinity iron permease essential for Candida albicans virulence","volume":"288","author":"Ramanan","year":"2000","journal-title":"Science"},{"key":"2021111618094879100_B32","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1046\/j.1365-2958.2002.02976.x","article-title":"Deletion of the copper transporter CaCCC2 reveals two distinct pathways for iron acquisition in Candida albicans","volume":"44","author":"Weissman","year":"2002","journal-title":"Mol. Microbiol."},{"key":"2021111618094879100_B33","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.fgb.2008.11.001","article-title":"Candida albicans cells lacking CaMCA1-encoded metacaspase show resistance to oxidative stress-induced death and change in energy metabolism","volume":"46","author":"Cao","year":"2009","journal-title":"Fungal. Genet. Biol."},{"key":"2021111618094879100_B34","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1128\/EC.00357-07","article-title":"Candida albicans Tup1 is involved in farnesol-mediated inhibition of filamentous-growth induction","volume":"7","author":"Kebaara","year":"2008","journal-title":"Eukaryot. Cell"},{"key":"2021111618094879100_B35","doi-asserted-by":"crossref","first-page":"1609","DOI":"10.1128\/IAI.01182-06","article-title":"Effect of farnesol on a mouse model of systemic candidiasis, determined by use of a DPP3 knockout mutant of Candida albicans","volume":"75","author":"Navarathna","year":"2007","journal-title":"Infect. Immun."},{"key":"2021111618094879100_B36","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/S1389-1723(02)80151-7","article-title":"Synergistic combination of direct plasma membrane damage and oxidative stress as a cause of antifungal activity of polyol macrolide antibiotic niphimycin","volume":"94","author":"Nakayama","year":"2002","journal-title":"J. Biosci. Bioeng."},{"key":"2021111618094879100_B37","doi-asserted-by":"crossref","first-page":"21592","DOI":"10.1074\/jbc.M608505200","article-title":"Miconazole induces changes in actin cytoskeleton prior to reactive oxygen species induction in yeast","volume":"282","author":"Thevissen","year":"2007","journal-title":"J. Biol. Chem."},{"key":"2021111618094879100_B38","doi-asserted-by":"crossref","first-page":"768","DOI":"10.7164\/antibiotics.56.768","article-title":"Apoptosis-like cell death of Saccharomyces cerevisiae induced by a mannose-binding antifungal antibiotic, pradimicin","volume":"56","author":"Hiramoto","year":"2003","journal-title":"J. Antibiot."},{"key":"2021111618094879100_B39","doi-asserted-by":"crossref","first-page":"7722","DOI":"10.1021\/jf0348774","article-title":"Perylenequinones act as broad-spectrum fungicides by generating reactive oxygen species both in the dark and in the light","volume":"51","author":"Xing","year":"2003","journal-title":"J. Agric. Food Chem."},{"key":"2021111618094879100_B40","doi-asserted-by":"crossref","first-page":"4460","DOI":"10.1128\/JB.180.17.4460-4465.1998","article-title":"Farnesol-induced generation of reactive oxygen species via indirect inhibition of the mitochondrial electron transport chain in the yeast Saccharomyces cerevisiae","volume":"180","author":"Machida","year":"1998","journal-title":"J. Bacteriol."},{"key":"2021111618094879100_B41","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1002\/pmic.200600575","article-title":"Proteomic analysis of the oxidative stress response in Candida albicans","volume":"7","author":"Kusch","year":"2007","journal-title":"Proteomics"},{"key":"2021111618094879100_B42","doi-asserted-by":"crossref","first-page":"2392","DOI":"10.1128\/AAC.01551-08","article-title":"Farnesol-induced apoptosis in Candida albicans","volume":"53","author":"Shirtliff","year":"2009","journal-title":"Antimicrob. Agents Chemother."},{"key":"2021111618094879100_B43","doi-asserted-by":"crossref","first-page":"3256","DOI":"10.1128\/AAC.01497-08","article-title":"Curcumin modulates efflux mediated by yeast ABC multidrug transporters and is synergistic with antifungals","volume":"53","author":"Sharma","year":"2009","journal-title":"Antimicrob. Agents Chemother."},{"key":"2021111618094879100_B44","doi-asserted-by":"crossref","first-page":"3695","DOI":"10.1128\/AAC.46.12.3695-3705.2002","article-title":"Drug susceptibilities of yeast cells are affected by membrane lipid composition","volume":"46","author":"Mukhopadhyay","year":"2002","journal-title":"Antimicrob. Agents Chemother."}],"container-title":["Bioscience Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/bioscirep\/article-pdf\/30\/6\/391\/474175\/bsr0300391.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/bioscirep\/article-pdf\/30\/6\/391\/474175\/bsr0300391.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,28]],"date-time":"2023-05-28T20:51:56Z","timestamp":1685307116000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/bioscirep\/article\/30\/6\/391\/55915\/Antifungal-curcumin-induces-reactive-oxygen"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,9,24]]},"references-count":44,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2010,12,1]]}},"URL":"https:\/\/doi.org\/10.1042\/bsr20090151","relation":{},"ISSN":["0144-8463","1573-4935"],"issn-type":[{"value":"0144-8463","type":"print"},{"value":"1573-4935","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,9,24]]}}}