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Toxins 2017, 9(9), 258; https://doi.org/10.3390/toxins9090258

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

1
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
2
Department of Pharmacology and Toxicology, University of Vienna, Althanstr. 14, 1090 Vienna, Austria
3
Department of Food Chemistry and Toxicology, Faculty of Pharmacy, University of Valencia, Av. Vicent A. Estellés s/n, 46100 Burjassot, Spain
4
Department of Agrobiotechnology (IFA-Tulln), University of Natural Resources and Life Sciences, Vienna (BOKU), Konrad Lorenz Str. 20, 3430 Tulln, Austria
5
Institut für Chemie, Technische Universität Berlin, Straße des 17. Juni 124, 10623 Berlin, Germany
6
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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Abstract

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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