Induction of apoptosis in yeast and mammalian cells by exposure to 1,10-phenanthroline metal complexes

Toxicol In Vitro. 2004 Feb;18(1):63-70. doi: 10.1016/j.tiv.2003.08.011.

Abstract

1,10-Phenanthroline (phen) and metal-phen complexes display fungicidal and fungiststic activity, disrupt mitochondrial function and induce oxidative stress. We have examined the effect of these drugs on the structure of yeast and mammalian cell organelles and the integrity of cellular DNA. Exposure of Candida albicans to [Mn(phen)2(mal)].2H2O or [Ag2(phen)3(mal)].2H2O (mal H2 = malonic acid) resulted in DNA degradation whereas exposure to phen or [Cu(phen)2(mal)].2H2O did not. All drugs induced extensive changes to the internal structure of yeast cells including retraction of the cytoplasm, nuclear fragmentation and disruption of the mitochondrion. In the case of cultured mammalian cells [Cu(phen)2(mal)].2H2O induced apoptosis as evidenced by the ladder pattern of DNA fragments following gel electrophoresis and also the blebbing of the cell membrane. The other drugs produced non-specific DNA degradation in mammalian cells. In conclusion, phen and metal-phen complexes have the potential to induce apoptosis in fungal and mammalian cells. Given their distinct mode of action compared to conventional anti-fungal drugs, phen and metal-phen complexes may represent a novel group of anti-fungal agents for use either in combination with existing drugs or in cases where resistance to conventional drugs has emerged.

Publication types

  • Comparative Study

MeSH terms

  • Antifungal Agents / adverse effects
  • Antifungal Agents / chemistry
  • Apoptosis / drug effects*
  • Candida albicans / drug effects
  • Candida albicans / genetics
  • Candida albicans / ultrastructure
  • Cell Line, Tumor*
  • Cell Membrane / drug effects
  • Cell Membrane / pathology
  • Cell Nucleus / drug effects
  • Cell Nucleus / pathology
  • Copper / chemistry
  • Culture Media
  • DNA Fragmentation / drug effects
  • DNA Fragmentation / genetics
  • DNA, Fungal / drug effects
  • DNA, Fungal / genetics
  • DNA, Fungal / isolation & purification
  • Humans
  • Manganese / chemistry
  • Microscopy, Electron, Scanning
  • Organometallic Compounds / adverse effects
  • Organometallic Compounds / chemistry
  • Phenanthrolines / adverse effects*
  • Phenanthrolines / chemistry
  • Silver / chemistry
  • Yeasts / drug effects
  • Yeasts / genetics

Substances

  • Antifungal Agents
  • Culture Media
  • DNA, Fungal
  • Organometallic Compounds
  • Phenanthrolines
  • Silver
  • Manganese
  • Copper