The Natural Fungal Metabolite Beauvericin Exerts Anticancer Activity In Vivo: A Pre-Clinical Pilot Study
Daniela Heilos,
Yelko Rodríguez-Carrasco,
Bernhard Englinger,
Gerald Timelthaler,
Sushilla van Schoonhoven,
Michael Sulyok,
Simon Boecker,
Roderich D. Süssmuth,
Petra Heffeter,
Rosa Lemmens-Gruber,
Rita Dornetshuber-Fleiss,
Walter Berger
Affiliations
Daniela Heilos
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
Yelko Rodríguez-Carrasco
Department of Food Chemistry and Toxicology, Faculty of Pharmacy, University of Valencia, Av. Vicent A. Estellés s/n, 46100 Burjassot, Spain
Bernhard Englinger
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
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 van Schoonhoven
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
Michael Sulyok
Department of Agrobiotechnology (IFA-Tulln), University of Natural Resources and Life Sciences, Vienna (BOKU), Konrad Lorenz Str. 20, 3430 Tulln, Austria
Simon Boecker
Institut für Chemie, Technische Universität Berlin, Straße des 17. Juni 124, 10623 Berlin, Germany
Roderich D. Süssmuth
Institut für Chemie, Technische Universität Berlin, Straße des 17. Juni 124, 10623 Berlin, Germany
Petra Heffeter
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
Rosa Lemmens-Gruber
Department of Pharmacology and Toxicology, University of Vienna, Althanstr. 14, 1090 Vienna, Austria
Rita Dornetshuber-Fleiss
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
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
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.
