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Emodin, a natural inhibitor of protein kinase CK2, suppresses growth, hyphal development, and biofilm formation of Candida albicans

Janeczko, Monika, Masłyk, Maciej, Kubiński, Konrad, Golczyk, Hieronim
Yeast 2017 v.34 no.6 pp. 253-265
Candida albicans, Rheum palmatum, antifungal properties, binding sites, biofilm, emodin, hyphae, immunosuppression, inhibitory concentration 50, minimum inhibitory concentration, models, phosphorylation, plant products, protein kinases, rhizomes, transcription factor NF-kappa B, vasodilation
Emodin (1,3,8‐trihydroxy‐6‐methyl‐anthraquinone) is a natural secondary plant product, originally isolated from the rhizomes of Rheum palmatum. Many reports show its diuretic, vasorelaxant, antibacterial, antiviral, anti‐ulcerogenic, immunosuppressive, hepatoprotective, anti‐inflammatory and anticancer potential. Emodin is a pleiotropic molecule capable of interacting with several major molecular targets, e.g. NF‐κB, AKT/mTOR and STAT3. The compound can also act as an inhibitor of some protein kinases, with special affinity to protein kinase CK2. The aim of the presented report was to evaluate antifungal properties of emodin and its activity towards CK2 isolated from Candida cells. Our studies revealed that the compound suppressed growth of the cells of reference strains as well as clinical Candida strains, with minimal inhibitory concentration and minimal fungicidal concentration values between 12.5 and 200 μg/mL. Moreover, at a low concentration, the compound was able to effectively stop hyphal formation, thus showing a distinct antivirulent potential. Interestingly, we showed that emodin added to Candida culture inhibited the phosphorylation of many cellular proteins, presumably owing to the inhibition of protein kinase CK2. Notably, the enzyme isolated from the Candida cells was susceptible to emodin with IC₅₀ of 2.8 μg/mL. Indeed, our computational modelling revealed that emodin was able to occupy the ATP‐binding pocket of CK2. Copyright © 2017 John Wiley & Sons, Ltd.