An atypical active cell death process underlies the fungicidal activity of ciclopirox olamine against the yeast Saccharomyces cerevisiae.
Ciclopirox olamine (CPO), a fungicidal agent widely used in clinical practice, induced in Saccharomyces cerevisiae an active cell death (ACD) process characterized by changes in nuclear morphology and chromatin condensation associated with the appearance of a population in the sub-G(0)/G(1) cell cycle phase and an arrest delay in the G(2)/M phases. This ACD was associated neither with intracellular reactive oxygen species (ROS) signaling, as revealed by the use of different classes of ROS scavengers, nor with a terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive phenotype. Furthermore, CPO-induced cell death seems to be dependent on unknown protease activity but independent of the apoptotic regulators Aif1p and Yca1p and of autophagic pathways involving Apg5p, Apg8p and Uth1p. Our results show that CPO triggers in S. cerevisiae an atypical nonapoptotic, nonautophagic ACD with as yet unknown regulators.
Almeida
Bruno
B
Life and Health Sciences Research Institute (ICVS), Health Sciences School, University of Minho, Campus de Gualtar, Braga, Portugal.
Sampaio-Marques
Belém
B
Carvalho
Joana
J
Silva
Manuel T
MT
Leão
Cecília
C
Rodrigues
Fernando
F
Ludovico
Paula
P
D000935:Antifungal Agents / Q000494:pharmacology*; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D000077768:Ciclopirox; D003513:Cycloheximide / Q000494:pharmacology; D005434:Flow Cytometry; D016166:Free Radical Scavengers / Q000494:pharmacology; D020287:In Situ Nick-End Labeling; D007700:Kinetics; D046529:Microscopy, Electron, Transmission; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000502:physiology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011728:Pyridones / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism
D000935:Antifungal Agents; D016166:Free Radical Scavengers; D011500:Protein Synthesis Inhibitors; D011728:Pyridones; D017382:Reactive Oxygen Species; D000077768:Ciclopirox; D003513:Cycloheximide; D016282:Aspartic Acid Endopeptidases