title: Photodynamic therapy with Pc 4 induces apoptosis of Candida albicans.
abstract: The high prevalence of drug resistance necessitates the development of novel antifungal agents against infections caused by opportunistic fungal pathogens, such as Candida albicans. Elucidation of apoptosis in yeast-like fungi may provide a basis for future therapies. In mammalian cells, photodynamic therapy (PDT) has been demonstrated to generate reactive oxygen species, leading to immediate oxidative modifications of biological molecules and resulting in apoptotic cell death. In this report, we assess the in vitro cytotoxicity and mechanism of PDT, using the photosensitizer Pc 4, in planktonic C. albicans. Confocal image analysis confirmed that Pc 4 localizes to cytosolic organelles, including mitochondria. A colony formation assay showed that 1.0 μM Pc 4 followed by light at 2.0 J cm(-2) reduced cell survival by 4 logs. XTT (2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxyanilide) assay revealed that Pc 4-PDT impaired fungal metabolic activity, which was confirmed using the FUN-1 (2-chloro-4-[2,3-dihydro-3-methyl-(benzo-1,3-thiazol-2-yl)-methylidene]-1-phenylquinolinium iodide) fluorescence probe. Furthermore, we observed changes in nuclear morphology characteristic of apoptosis, which were substantiated by increased externalization of phosphatidylserine and DNA fragmentation following Pc 4-PDT. These data indicate that Pc 4-PDT can induce apoptosis in C. albicans. Therefore, a better understanding of the process will be helpful, as PDT may become a useful treatment option for candidiasis.
authors.affiliation: Department of Dermatology, University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Minh
authors.initials: M
authors.lastname: Lam
authors.forename: Paul C
authors.initials: PC
authors.lastname: Jou
authors.forename: Ali A
authors.initials: AA
authors.lastname: Lattif
authors.forename: Yoojin
authors.initials: Y
authors.lastname: Lee
authors.forename: Christi L
authors.initials: CL
authors.lastname: Malbasa
authors.forename: Pranab K
authors.initials: PK
authors.lastname: Mukherjee
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Oleinick
authors.forename: Mahmoud A
authors.initials: MA
authors.lastname: Ghannoum
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Cooper
authors.forename: Elma D
authors.initials: ED
authors.lastname: Baron
mesh_terms: D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D002176:Candida albicans / Q000187:drug effects* / Q000254:growth & development / Q000528:radiation effects*; D002177:Candidiasis / Q000188:drug therapy* / Q000382:microbiology; D015169:Colony Count, Microbial; D053938:DNA Fragmentation / Q000187:drug effects / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D005453:Fluorescence; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology*; D008027:Light; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D017646:Organosilicon Compounds / Q000737:chemistry / Q000494:pharmacology*; D010718:Phosphatidylserines / Q000378:metabolism; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000737:chemistry / Q000494:pharmacology*; D010933:Plankton / Q000187:drug effects / Q000254:growth & development / Q000528:radiation effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D013778:Tetrazolium Salts / Q000032:analysis
chemical_list: D000935:Antifungal Agents; D007211:Indoles; D017646:Organosilicon Compounds; D010718:Phosphatidylserines; D017319:Photosensitizing Agents; D017382:Reactive Oxygen Species; D013778:Tetrazolium Salts; C059087:2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-((phenylamino)carbonyl)-2H-tetrazolium hydroxide; C082854:silicon phthalocyanine