An Atypical Active Cell Death Process Underlies the Fungicidal Activity of Ciclopirox Olamine Against the Yeast Saccharomyces Cerevisiae

FEMS Yeast Res. 2007 May;7(3):404-12. doi: 10.1111/j.1567-1364.2006.00188.x. Epub 2007 Jan 19.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antifungal Agents / pharmacology*
  • Aspartic Acid Endopeptidases / metabolism
  • Cell Cycle / drug effects
  • Cell Cycle / physiology
  • Cell Membrane / drug effects
  • Cell Membrane / physiology
  • Ciclopirox
  • Cycloheximide / pharmacology
  • Flow Cytometry
  • Free Radical Scavengers / pharmacology
  • In Situ Nick-End Labeling
  • Kinetics
  • Microscopy, Electron, Transmission
  • Mitochondrial Membranes / drug effects
  • Mitochondrial Membranes / physiology
  • Protein Synthesis Inhibitors / pharmacology
  • Pyridones / pharmacology*
  • Reactive Oxygen Species / metabolism
  • Saccharomyces cerevisiae / cytology*
  • Saccharomyces cerevisiae / drug effects*
  • Saccharomyces cerevisiae / growth & development
  • Saccharomyces cerevisiae / metabolism

Substances

  • Antifungal Agents
  • Free Radical Scavengers
  • Protein Synthesis Inhibitors
  • Pyridones
  • Reactive Oxygen Species
  • Ciclopirox
  • Cycloheximide
  • Aspartic Acid Endopeptidases