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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 Ca 2+ 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 Ca 2+ 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.

The six transmembrane protein of prostate 2 (STAMP2) is an androgen-regulated gene whose mRNA expression is increased in prostate cancer (PCa). Here, we show that STAMP2 protein expression is increased in human PCa compared with benign prostate that is also correlated with tumor grade and treatment response. We also show that STAMP2 significantly increased reactive oxygen species (ROS) in PCa cells through its iron reductase activity which also depleted NADPH levels. Knockdown of STAMP2 expression in PCa cells inhibited proliferation, colony formation, and anchorage-independent growth, and significantly increased apoptosis. Furthermore, STAMP2 effects were, at least in part, mediated by activating transcription factor 4 (ATF4), whose expression is regulated by ROS. Consistent with in vitro findings, silencing STAMP2 significantly inhibited PCa xenograft growth in mice. Finally, therapeutic silencing of STAMP2 by systemically administered nanoliposomal siRNA profoundly inhibited tumor growth in two established preclinical PCa models in mice. These data suggest that STAMP2 is required for PCa progression and thus may serve as a novel therapeutic target., (© 2015 The Authors. Published under the terms of the CC BY 4.0 license.)

Vulvovaginal candidiasis (VVC) is one of the most frequent diseases induced by Candida albicans (C. albicans) during pregnancy, which results in enormous pain to women and their partners in daily life. Perillaldehyde (PAE), a natural monoterpenoid, has significant anti-microbial, anti-inflammatory and anti-oxidation effects. Reactive oxygen species (ROS) are key factors for the host to resist the invasion of fungi. However, excess ROS can cause additional damage independent of the pathogen itself, and the mechanism of ROS in VVC has not been investigated. In this murine study, we revealed that C. albicans infection increased the expression of NADPH oxidase 2 (NOX2) and the content of malonaldehyde (MDA). C. albicans inhibited the activity of antioxidant enzymes in the vagina, including superoxide dismutase (SOD), Catalase (CAT), glutathione peroxidase (GSH-PX) and heme oxygenase (HO-1), which were returned to normal levels after treatment with PAE. Furthermore, PAE inhibited the activities of Keap1 and promoted Nrf2 transfer from cytoplasm to nucleus, which were mediated by excessive accumulation of ROS in the VVC mice. In this study, we also indicated that PAE inhibited the apoptosis of vagina cells via Caspase 9- Caspase 7-PARP pathway and prevented the release of IL-1ꞵ in VVC mice. In summary, this study revealed that the treatment of VVC in mice with PAE might be mediated by inhibition of ROS, and established the therapeutic potential of PAE as an antifungal agent for the treatment of VVC. [ABSTRACT FROM AUTHOR]

A correction to the article "Calcium and oxidative stress mediate perillaldehyde-induced apoptosis in Candida albicans,"