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Calcium and oxidative stress mediate perillaldehyde-induced apoptosis in Candida albicans

Tian, Hui, Qu, Su, Wang, Yanzhen, Lu, Zhaoqun, Zhang, Man, Gan, Yeyun, Zhang, Peng, Tian, Jun
Applied microbiology and biotechnology 2017 v.101 no.8 pp. 3335-3345
Candida albicans, DNA damage, Perilla frutescens, Western blotting, antifungal properties, apoptosis, calcium, cytochrome c, drugs, flow cytometry, fluorescence microscopy, mechanism of action, membrane potential, minimum inhibitory concentration, mitochondrial membrane, monoterpenoids, oxidative stress, phosphatidylserines
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.