Coyle, Barry and Kinsella, Paula and McCann, Malachy and Devereux, Michael and O'Connor, Robert and Clynes, Martin and Kavanagh, Kevin
Induction of apoptosis in yeast and mammalian cells by exposure to 1,10-phenanthroline metal complexes.
Toxicology in Vitro, 18 (1).
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.
||Apoptosis; Candida; Metal-based drug; Fungicidal; Fungistatic;
||Faculty of Science and Engineering > Biology
Dr. Kevin Kavanagh
||01 Feb 2005
|Journal or Publication Title:
||Toxicology in Vitro
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