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Toxins 2017, 9(9), 258;

The Natural Fungal Metabolite Beauvericin Exerts Anticancer Activity In Vivo: A Pre-Clinical Pilot Study

Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, and Comprehensive Cancer Center of the Medical University, Borschkegasse 8a, 1090 Vienna, Austria
Department of Pharmacology and Toxicology, University of Vienna, Althanstr. 14, 1090 Vienna, Austria
Department of Food Chemistry and Toxicology, Faculty of Pharmacy, University of Valencia, Av. Vicent A. Estellés s/n, 46100 Burjassot, Spain
Department of Agrobiotechnology (IFA-Tulln), University of Natural Resources and Life Sciences, Vienna (BOKU), Konrad Lorenz Str. 20, 3430 Tulln, Austria
Institut für Chemie, Technische Universität Berlin, Straße des 17. Juni 124, 10623 Berlin, Germany
Research Cluster “Translational Cancer Therapy Research”, 1090 Vienna, Austria
Author to whom correspondence should be addressed.
Academic Editor: Annie Pfohl-Leszkowicz
Received: 28 April 2017 / Revised: 27 July 2017 / Accepted: 22 August 2017 / Published: 24 August 2017
(This article belongs to the Section Mycotoxins)
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Recently, in vitro anti-cancer properties of beauvericin, a fungal metabolite were shown in various cancer cell lines. In this study, we assessed the specificity of this effect by comparing beauvericin cytotoxicity in malignant versus non-malignant cells. Moreover, we tested in vivo anticancer effects of beauvericin by treating BALB/c and CB-17/SCID mice bearing murine CT-26 or human KB-3-1-grafted tumors, respectively. Tumor size and weight were measured and histological sections were evaluated by Ki-67 and H/E staining as well as TdT-mediated-dUTP-nick-end (TUNEL) labeling. Beauvericin levels were determined in various tissues and body fluids by LC-MS/MS. In addition to a more pronounced activity against malignant cells, we detected decreased tumor volumes and weights in beauvericin-treated mice compared to controls in both the allo- and the xenograft model without any adverse effects. No significant differences were detected concerning percentages of proliferating and mitotic cells in tumor sections from treated and untreated mice. However, a significant increase of necrotic areas within whole tumor sections of beauvericin-treated mice was found in both models corresponding to an enhanced number of TUNEL-positive, i.e., apoptotic, cells. Furthermore, moderate beauvericin accumulation was detected in tumor tissues. In conclusion, we suggest beauvericin as a promising novel natural compound for anticancer therapy. View Full-Text
Keywords: cyclohexadepsipeptide; beauvericin; cervix carcinoma; colorectal carcinoma; therapy cyclohexadepsipeptide; beauvericin; cervix carcinoma; colorectal carcinoma; therapy

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Heilos, D.; Rodríguez-Carrasco, Y.; Englinger, B.; Timelthaler, G.; van Schoonhoven, S.; Sulyok, M.; Boecker, S.; Süssmuth, R.D.; Heffeter, P.; Lemmens-Gruber, R.; Dornetshuber-Fleiss, R.; Berger, W. The Natural Fungal Metabolite Beauvericin Exerts Anticancer Activity In Vivo: A Pre-Clinical Pilot Study. Toxins 2017, 9, 258.

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