Anatypical active cell death process underlies the fungicidal activity of ciclopiroxolamine against the yeast Saccharomyces cerevisiae

摘要

Ciclopirox olamine (CPO), a fungicidal agent widely used in clinical practice,induced in Saccharomyces cerevisiae an active cell death (ACD) process characterizedby changes in nuclear morphology and chromatin condensation associatedwith the appearance of a population in the sub-G0/G1 cell cycle phase and an arrestin the G2/M phases. This ACD was associated neither with intracellular reactiveoxygen species (ROS) signaling, as revealed by the use of different classes of ROSscavengers, nor with a terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive phenotype. Furthermore, CPO-induced cell deathseems to be dependent on unknown protease activity but independent of the apoptotic regulators Aif1p and Yca1p and of autophagic pathways involvingApg5p, Apg8p and Uth1p. Our results show that CPO triggers in S. cerevisiae anatypical nonapoptotic, nonautophagic ACD with as yet unknown regulators.