Amentoflavone stimulates mitochondrial dysfunction and induces apoptotic cell death in Candida albicans.
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.
School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University, Daehak-ro 80, Buk-gu, Daegu, Republic of Korea.
In-Sok
IS
Hwang
Juneyoung
J
Lee
Hong-Guang
HG
Jin
Eun-Rhan
ER
Woo
Dong Gun
DG
Lee
D000935:Antifungal Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D044946:Biflavonoids / Q000494:pharmacology*; D002176:Candida albicans / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D002177:Candidiasis / Q000188:drug therapy / Q000382:microbiology; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D032503:Selaginellaceae / Q000737:chemistry*
D000935:Antifungal Agents; D044946:Biflavonoids; D010936:Plant Extracts; D017382:Reactive Oxygen Species; C011164:amentoflavone