Amentoflavone Stimulates Mitochondrial Dysfunction and Induces Apoptotic Cell Death in Candida albicans
- 31 December 2011
- journal article
- research article
- Published by Springer Science and Business Media LLC in Mycopathologia
- Vol. 173 (4), 207-218
- https://doi.org/10.1007/s11046-011-9503-x
Abstract
Amentoflavone was isolated from an ethyl acetate extract of the whole plant of Selaginella tamariscina. It is a traditional herb for the therapy of chronic trachitis and exhibits some anti-tumor activity. Previously, we confirmed the antifungal effects of amentoflavone. The objective of this study was to investigate the antifungal mechanism(s) of amentoflavone, such as mitochondria-mediated apoptotic cell death. The cells that were treated with amentoflavone exhibited a series of cellular changes that were consistent with apoptosis: externalization of phosphatidylserine, DNA and nuclear fragmentation, accumulation of intracellular reactive oxygen species (ROS) and hydroxyl radicals, and activation of metacaspase. In addition, diagnostic markers of apoptosis, including the reduction of mitochondrial inner-membrane potential and the release of cytochrome c from mitochondria, were observed. These phenomena are important changes in mitochondria-mediated apoptosis. Furthermore, the effect of thiourea as hydroxyl radical scavenger on amentoflavone-induced apoptosis was evaluated. A hydroxyl radical is a more active ROS species. Mitochondrial dysfunction was inhibited, which was indicated by decreased levels of intracellular hydroxyl radicals. Taken together, our results present the first evidence that amentoflavone induces apoptosis in C. albicans cells and is associated with the mitochondrial dysfunction. Besides, amentoflavone-induced hydroxyl radicals may play a significant role in mitochondria-mediated apoptosis.Keywords
This publication has 49 references indexed in Scilit:
- Plagiochin E, an antifungal active macrocyclic bis(bibenzyl), induced apoptosis in Candida albicans through a metacaspase-dependent apoptotic pathwayBiochimica et Biophysica Acta (BBA) - General Subjects, 2010
- Monitoring Singlet Oxygen and Hydroxyl Radical Formation with Fluorescent Probes During Photodynamic TherapyPhotochemistry and Photobiology, 2009
- ADP/ATP carrier is required for mitochondrial outer membrane permeabilization and cytochrome c release in yeast apoptosisMolecular Microbiology, 2007
- Non-apoptotic Phosphatidylserine Externalization Induced by Engagement of Glycosylphosphatidylinositol-anchored ProteinsPublished by Elsevier BV ,2007
- Characterization of DNA Damage in Yeast Apoptosis Induced by Hydrogen Peroxide, Acetic Acid, and Hyperosmotic ShockMolecular Biology of the Cell, 2006
- Induction of apoptosis by spermine-metabolites in primary human blood cells and various tumor cell linesApoptosis, 2005
- CytochromecRelease and Mitochondria Involvement in Programmed Cell Death Induced by Acetic Acid inSaccharomyces cerevisiaeMolecular Biology of the Cell, 2002
- A Yeast Mutant Showing Diagnostic Markers of Early and Late ApoptosisThe Journal of cell biology, 1997
- Thiourea and Dimethylthiourea Inhibit Peroxynitrite-Dependent Damage: Nonspecificity as Hydroxyl Radical ScavengersFree Radical Biology & Medicine, 1997
- Inhibitors of permeability transition interfere with the disruption of the mitochondrial transmembrane potential during apoptosisFEBS Letters, 1996