Calcium and oxidative stress mediate perillaldehyde-induced apoptosis in Candida albicans |
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Authors: | Tian Hui Qu Su Wang Yanzhen Lu Zhaoqun Zhang Man Gan Yeyun Zhang Peng Tian Jun |
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Affiliation: | 1.College of Life Science, Jiangsu Normal University, Xuzhou, 221116, Jiangsu Province, People’s Republic of China ;2.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 ; |
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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. |
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