Drug repurposing against Candida auris: A systematic review.

Candida auris is a drug-resistant pathogen with several reported outbreaks. The treatment of C. auris infections is difficult due to a limited number of available antifungal drugs. Thus, finding alternative drugs through repurposing approaches would be clinically beneficial. A systematic search in PubMed, Scopus and Web of Science databases, as well as Google Scholar up to 1 November 2021, was conducted to find all articles with data regarding the antifungal activity of non-antifungal drugs against the planktonic and biofilm forms of C. auris. During database and hand searching, 290 articles were found, of which 13 were eligible for inclusion in the present study. Planktonic and biofilm forms have been studied in 11 and 8 articles (with both forms examined in 6 articles), respectively. In total, 22 and 12 drugs/compounds have been reported as repositionable against planktonic and biofilm forms of C. auris, respectively. Antiparasitic drugs, with the dominance of miltefosine, were the most common repurposed drugs against both forms of C. auris, followed by anticancer drugs (e.g. alexidine dihydrochloride) against the planktonic form and anti-inflammatory drugs (e.g. ebselen) against the biofilm form of the fungus. A collection of other drugs from various classes have also shown promising activity against C. auris. Following drug repurposing approaches, a number of drugs/compounds from various classes have been found to inhibit the planktonic and biofilm forms of C. auris. Accordingly, drug repurposing is an encouraging approach for discovering potential alternatives to conventional antifungal agents to combat drug resistance in fungi, especially C. auris.

The effect of Candida cell wall beta-glucan on treatment-resistant LL/2 cancer cell line: in vitro evaluation.

Candida albicans (C. albicans) cell wall beta-glucan has been considered as a potential agent in the treatment of cancers due to its anti-tumor properties. Therefore, in the present study, we investigated the anti-cancer effects of Candida cell wall beta-glucan on Lewis lung carcinoma cell line (LL/2) cells. Beta-glucan of C. albicans cell wall was extracted. LL/2 cell line was cultured, then sphere cells and parental cells were exposed to the different concentrations of beta-glucan extracted from C. albicans (10-6000 µg/ml), for 24, 48 and 72 h. Cytotoxicity of beta-glucan was assayed by MTT test, then RNA extracted from cells population (treated and untreated cells), cDNA synthetized and expression level of Sox2, Oct4, C-myc, Nanog genes were also investigated using Real-time methods. At optimal concentrations of 800 and 1000 µg/ml, the extracted beta-glucan showed a significant cytotoxic effect on both parental and sphere cell populations (p < 0.05). Real-time PCR analysis revealed a decreased expression of Oct4 and Sox2 genes in treatment of cells with beta-glucan compared with control group. Since the extracted beta-glucan showed an inhibitory effect on the expression of Oct4 and Sox2 genes involved in LL/2 metastasis, therefore, beta-glucan can be considered as an anti-tumor agent because of its anti-metastatic properties, however, more in vitro and in vivo studies are needed to provide further evidence on this topic in the future.

Candida albicans Beta-Glucan Induce Anti- Cancer Activity of Mesenchymal Stem Cells against Lung Cancer Cell Line: An In-Vitro Experimental Study.

OBJECTIVE: ß-glucan, glucopyranosyl polymers of fungi cell wall, represent an immune stimulating effects with potential anti-cancer activity. Mesenchymal stem cells (MSC) have immunomodulating properties in cancer microenvironment. The aim of this study was to investigate the anti-cancer effect of Candida albicans (C. albicans) beta-glucan on MSCs supernatant for apoptosis assay of lung cancer cells in vitro. METHODS: Beta-glucan was extracted from cell wall of C.albicans. MSC isolated from adipose tissue of patients and confirmed using specific surface markers expression which examined by flow cytometry. MSCs treated with various concentrations of ß-glucans for 48 hours. Cytotoxic effect of ß-glucans was evaluated using MTT assay. MSC and lung cancer line cocultured and treated with ß-glucans and apoptosis assay was done by flow cytometry. RESULTS: Cytotoxicity findings showed a significant decrease in MSC viability during 48h, however it was dose-dependent (P<0.05). According to the obtained findings, supernatant of mesenchymal stem cells treated with ß-glucans increased cancer cells apoptosis (P<0.05). CONCLUSION: Beta glucan may highlight a potential and novel promising candidate in future strategies to cause apoptosis of cancer cells and consider as therapeutic  agent against tumor growth as well. Definitely, more in vitro and in vivo studies are required to understand its functions.