title: Role of potassium channels in chlorogenic acid-induced apoptotic volume decrease and cell cycle arrest in Candida albicans.
abstract: Chlorogenic acid (CRA) is an abundant phenolic compound in the human diet. CRA has a potent antifungal effect, inducing cell death in Candida albicans. However, there are no further studies to investigate the antifungal mechanism of CRA, associated with ion channels.
  
  
  
  To evaluate the inhibitory effects on CRA-induced cell death, C. albicans cells were pretreated with potassium and chloride channel blockers, separately. Flow cytometry was carried out to detect several hallmarks of apoptosis, such as cell cycle arrest, caspase activation, and DNA fragmentation, after staining of the cells with SYTOX green, FITC-VAD-FMK, and TUNEL.
  
  
  
  CRA caused excessive potassium efflux, and an apoptotic volume decrease (AVD) was observed. This change, in turn, induced cytosolic calcium uptake and cell cycle arrest in C. albicans. Moreover, CRA induced caspase activation and DNA fragmentation, which are considered apoptotic markers. In contrast, the potassium efflux and proapoptotic changes were inhibited when potassium channels were blocked, whereas there was no inhibitory effect when chloride channels were blocked.
  
  
  
  CRA induces potassium efflux, leading to AVD and G2/M cell cycle arrest in C. albicans. Therefore, potassium efflux via potassium channels regulates the CRA-induced apoptosis, stimulating several apoptotic processes.
  
  
  
  This study improves the understanding of the antifungal mechanism of CRA and its association with ion homeostasis, thereby pointing to a role of potassium channels in CRA-induced apoptosis.
authors.affiliation: School of Life Sciences, BK 21 Plus KNU Creative BioResearch Group, College of Natural Sciences, Kyungpook National University, 80 Daehakro, Bukgu, Daegu 41566, Republic of Korea.
authors.forename: JiEun
authors.initials: J
authors.lastname: Yun
authors.affiliation: School of Life Sciences, BK 21 Plus KNU Creative BioResearch Group, College of Natural Sciences, Kyungpook National University, 80 Daehakro, Bukgu, Daegu 41566, Republic of Korea.. Electronic address: dglee222@knu.ac.kr.
authors.forename: Dong Gun
authors.initials: DG
authors.lastname: Lee
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D015415:Biomarkers / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002176:Candida albicans / Q000187:drug effects* / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D018118:Chloride Channels / Q000037:antagonists & inhibitors*; D002726:Chlorogenic Acid / Q000494:pharmacology*; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D015221:Potassium Channels / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000935:Antifungal Agents; D015415:Biomarkers; D018118:Chloride Channels; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D017382:Reactive Oxygen Species; D002726:Chlorogenic Acid; D002118:Calcium
keywords: Apoptotic volume decrease; Cell cycle arrest; Chlorogenic acid; Potassium channel