title: Calcium and oxidative stress mediate perillaldehyde-induced apoptosis in Candida albicans.
abstract: New anti-Candida albicans drugs are needed due to the emergence of resistant cases in recent years. Perillaldehyde (PAE) is a natural monoterpenoid compound derived from Perilla frutescens. The minimum inhibitory concentration of PAE against C. albicans was 0.4 μL/mL. We aimed to elucidate the antifungal mode of action of PAE against C. albicans. The antifungal activity of PAE against C. albicans was found to correlate with an elevation in intracellular Ca2+and accumulation of ROS. Several downstream apoptosis events such as the disruption of mitochondrial membrane potential, phosphatidylserine externalization, cytochrome c release, and metacaspase activation were observed in PAE-treated cells. DNA damage and nuclear fragmentation assays also revealed apoptosis of C. albicans cells. In summary, by means of fluorescent microscopy, flow cytometer analysis, and Western blot, our data uncovered that PAE exerts its antifungal activity through Ca2+and oxidative stress-mediated apoptosis mechanisms. This study deciphered the mode of action of PAE, which will be useful in the design of improved antifungal therapies.
authors.affiliation: College of Life Science, Jiangsu Normal University, Xuzhou, 221116, Jiangsu Province, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Tian
authors.affiliation: College of Life Science, Jiangsu Normal University, Xuzhou, 221116, Jiangsu Province, People's Republic of China.
authors.forename: Su
authors.initials: S
authors.lastname: Qu
authors.affiliation: College of Life Science, Jiangsu Normal University, Xuzhou, 221116, Jiangsu Province, People's Republic of China.
authors.forename: Yanzhen
authors.initials: Y
authors.lastname: Wang
authors.affiliation: College of Life Science, Jiangsu Normal University, Xuzhou, 221116, Jiangsu Province, People's Republic of China.
authors.forename: Zhaoqun
authors.initials: Z
authors.lastname: Lu
authors.affiliation: College of Life Science, Jiangsu Normal University, Xuzhou, 221116, Jiangsu Province, People's Republic of China.
authors.forename: Man
authors.initials: M
authors.lastname: Zhang
authors.affiliation: College of Life Science, Jiangsu Normal University, Xuzhou, 221116, Jiangsu Province, People's Republic of China.
authors.forename: Yeyun
authors.initials: Y
authors.lastname: Gan
authors.affiliation: College of Life Science, Jiangsu Normal University, Xuzhou, 221116, Jiangsu Province, People's Republic of China. zhangpeng@jsnu.edu.cn.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: College of Life Science, Jiangsu Normal University, Xuzhou, 221116, Jiangsu Province, People's Republic of China. tj-085@163.com.|Key Lab for New Drug Research of TCM and Shenzhen Branch, State R&D Centre for Viro-Biotech, Research Institute of Tsinghua University in Shenzhen, Shenzhen, Guangdong, People's Republic of China. tj-085@163.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Tian
mesh_terms: D017209:Apoptosis; D002118:Calcium / Q000378:metabolism*; D002176:Candida albicans / Q000187:drug effects* / Q000502:physiology; D045304:Cytochromes c / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D005434:Flow Cytometry; D008826:Microbial Sensitivity Tests; D008856:Microscopy, Fluorescence; D039821:Monoterpenes / Q000494:pharmacology*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D039821:Monoterpenes; D017382:Reactive Oxygen Species; C033342:perillaldehyde; D045304:Cytochromes c; D002118:Calcium
keywords: Antifungal; Apoptosis; Calcium; Candida albicans; Oxidative stress; Perillaldehyde