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

Abstract

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 IC 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.

Synthesis and Antimicrobial Evaluation of 1,4‐Naphthoquinone Derivatives as Potential Antibacterial Agents

“…The in vitro antimicrobial study was performed using the microbroth dilution method against tested organisms, followed by a previously described method ,. The bacterial culture was inoculated in Mueller Hinton Broth medium (Biocorp, Warsaw, Poland) and incubated at 37 °C and with vigorous shaking (200 rpm) for 24‐h.…”

“…The in vitro antimicrobial study was performed using the microbroth dilution method against tested organisms, followed by a previously described method. [37,38] The bacterial culture was inoculated in Mueller Hinton Broth medium (Biocorp, Warsaw, Poland) and incubated at 37°C and with vigorous shaking (200 rpm) for 24h. Bacterial cell suspensions at initial inoculums of 5 × 10 5 in Mueller-Hinton liquid medium were exposed to the examined compounds at relevant concentrations (range, 0.001-2 mg/mL) for 24-h at 37°C.…”

Silymarin, a Popular Dietary Supplement Shows Anti–Candida Activity

“…The ability to adhere to host tissues has been described in all species of the Candida genus, but in comparison with C. albicans, C. tropicalis, and C. parapsilosis, lower adhesive properties have been detected in C. glabrata [6,15]. In the recent years, many efforts have been made to explore new and effective natural compounds with anti-adhesion and anti-biofilm development effects [7,[16][17][18]. Tests As demonstrated in previous studies on natural compounds, phenols such as flavonoids and lignans have shown their antimicrobial potential [7].…”

Aspartate semialdehyde dehydrogenase inhibition suppresses the growth of the pathogenic fungus Candida albicans

“…Candida albicans is a common, opportunistic human fungal pathogen that can cause both mucosal and deep tissue infections (Janeczko, Maslyk, Kubinski, & Golczyk, 2017), and is the most frequently isolated fungus from clinical settings (Leite, de Brito Bezerra, de Sousa, & de Oliveira Lima, 2015). C .…”

“…albicans inhabits the body as a commensal, but during immunosuppression, it is the causative agent of human candidiasis (Lopez‐Martinez, 2010) and can also cause including potentially life‐threatening blood‐borne infections. The Candida genus includes about 20 different Candida species that are known to be etiological agents of human infections (Janeczko et al, 2017), and many fungal species are developing resistance to commonly prescribed antifungal agents (Ellis, 2002). The threat from Candida species is especially serious in immunocompromised patients, including organ transplant recipients, patients receiving cancer radiotherapy or chemotherapy, and HIV/AIDS patients (Leite et al, 2015).…”