title: Garcinia xanthochymus Benzophenones Promote Hyphal Apoptosis and Potentiate Activity of Fluconazole against Candida albicans Biofilms.
abstract: Xanthochymol and garcinol, isoprenylated benzophenones purified from Garcinia xanthochymus fruits, showed multiple activities against Candida albicans biofilms. Both compounds effectively prevented emergence of fungal germ tubes and were also cytostatic, with MICs of 1 to 3 μM. The compounds therefore inhibited development of hyphae and subsequent biofilm maturation. Xanthochymol treatment of developing and mature biofilms induced cell death. In early biofilm development, killing had the characteristics of apoptosis, including externalization of phosphatidyl serine and DNA fragmentation, as evidenced by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) fluorescence. These activities resulted in failure of biofilm maturation and hyphal death in mature biofilms. In mature biofilms, xanthochymol and garcinol caused the death of biofilm hyphae, with 50% effective concentrations (EC50s) of 30 to 50 μM. Additionally, xanthochymol-mediated killing was complementary with fluconazole against mature biofilms, reducing the fluconazole EC50 from >1,024 μg/ml to 13 μg/ml. Therefore, xanthochymol has potential as an adjuvant for antifungal treatments as well as in studies of fungal apoptosis.
authors.affiliation: Biology Department, Brooklyn College of the City University of New York, New York, New York, USA.
authors.forename: Desmond N
authors.initials: DN
authors.lastname: Jackson
authors.affiliation: Biology Department, Brooklyn College of the City University of New York, New York, New York, USA The Graduate Center of the City University of New York, New York, New York, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Biological Sciences, Lehman College of the City University of New York, New York, New York, USA.
authors.forename: ShiBiao
authors.initials: S
authors.lastname: Wu
authors.affiliation: The Graduate Center of the City University of New York, New York, New York, USA Department of Biological Sciences, Lehman College of the City University of New York, New York, New York, USA.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Kennelly
authors.affiliation: Biology Department, Brooklyn College of the City University of New York, New York, New York, USA The Graduate Center of the City University of New York, New York, New York, USA plipke@brooklyn.cuny.edu.
authors.forename: Peter N
authors.initials: PN
authors.lastname: Lipke
mesh_terms: D000935:Antifungal Agents / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001577:Benzophenones / Q000302:isolation & purification / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development; D002176:Candida albicans / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D004338:Drug Combinations; D004357:Drug Synergism; D015725:Fluconazole / Q000494:pharmacology; D005638:Fruit / Q000737:chemistry; D029760:Garcinia / Q000737:chemistry*; D025301:Hyphae / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D008826:Microbial Sensitivity Tests; D010718:Phosphatidylserines / Q000037:antagonists & inhibitors / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry; D013729:Terpenes / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D000935:Antifungal Agents; D001577:Benzophenones; D004338:Drug Combinations; D010718:Phosphatidylserines; D010936:Plant Extracts; D013729:Terpenes; C414432:xanthochymol; D015725:Fluconazole; C054597:garcinol