2. Academic Validation
  3. The Natural Fungal Metabolite Beauvericin Exerts Anticancer Activity In Vivo: A Pre-Clinical Pilot Study

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

  • Toxins (Basel). 2017 Aug 24;9(9):258. doi: 10.3390/toxins9090258.
Daniela Heilos 1 2,  Yelko Rodríguez-Carrasco 3,  Bernhard Englinger 4,  Gerald Timelthaler 5,  Sushilla van Schoonhoven 6,  Michael Sulyok 7,  Simon Boecker 8,  Roderich D Süssmuth 9,  Petra Heffeter 10 11,  Rosa Lemmens-Gruber 12,  Rita Dornetshuber-Fleiss 13 14,  Walter Berger 15 16
Affiliations

Affiliations

  • 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. daniela.heilos@univie.ac.at.
  • 2 Department of Pharmacology and Toxicology, University of Vienna, Althanstr. 14, 1090 Vienna, Austria. daniela.heilos@univie.ac.at.
  • 3 Department of Food Chemistry and Toxicology, Faculty of Pharmacy, University of Valencia, Av. Vicent A. Estellés s/n, 46100 Burjassot, Spain. yelko.rodriguez@uv.es.
  • 4 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. bernhard.englinger@meduniwien.ac.at.
  • 5 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. gerald.timelthaler@meduniwien.ac.at.
  • 6 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. sushilla.vanschoonhoven@meduniwien.ac.at.
  • 7 Department of Agrobiotechnology (IFA-Tulln), University of Natural Resources and Life Sciences, Vienna (BOKU), Konrad Lorenz Str. 20, 3430 Tulln, Austria. michael.sulyok@boku.ac.at.
  • 8 Institut für Chemie, Technische Universität Berlin, Straße des 17. Juni 124, 10623 Berlin, Germany. simon.boecker@chem.tu-berlin.de.
  • 9 Institut für Chemie, Technische Universität Berlin, Straße des 17. Juni 124, 10623 Berlin, Germany. suessmuth@chem.tu-berlin.de.
  • 10 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. petra.heffeter@meduniwien.ac.at.
  • 11 Research Cluster "Translational Cancer Therapy Research", 1090 Vienna, Austria. petra.heffeter@meduniwien.ac.at.
  • 12 Department of Pharmacology and Toxicology, University of Vienna, Althanstr. 14, 1090 Vienna, Austria. rosa.lemmens@univie.ac.at.
  • 13 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. rita.dornetshuber@univie.ac.at.
  • 14 Department of Pharmacology and Toxicology, University of Vienna, Althanstr. 14, 1090 Vienna, Austria. rita.dornetshuber@univie.ac.at.
  • 15 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. walter.berger@meduniwien.ac.at.
  • 16 Research Cluster "Translational Cancer Therapy Research", 1090 Vienna, Austria. walter.berger@meduniwien.ac.at.
PMID: 28837057 DOI: 10.3390/toxins9090258
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.

Keywords

beauvericin; cervix carcinoma; colorectal carcinoma; cyclohexadepsipeptide; therapy.

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