Synergistic Antitumour Properties of viscumTT in Alveolar Rhabdomyosarcoma
Aqueous mistletoe extracts from the European mistletoe (Viscum album) contain mainly mistletoe lectins and viscotoxins as cytotoxic compounds. Lipophilic triterpene acids, which do not occur in conventional mistletoe preparations, were solubilised with β-cyclodextrins. The combination of an aqueous...
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2017-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2017/4874280 |
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| author | Rahel Mascha Stammer Susann Kleinsimon Jana Rolff Sebastian Jäger Angelika Eggert Georg Seifert Catharina I. Delebinski |
| author_facet | Rahel Mascha Stammer Susann Kleinsimon Jana Rolff Sebastian Jäger Angelika Eggert Georg Seifert Catharina I. Delebinski |
| author_sort | Rahel Mascha Stammer |
| collection | DOAJ |
| description | Aqueous mistletoe extracts from the European mistletoe (Viscum album) contain mainly mistletoe lectins and viscotoxins as cytotoxic compounds. Lipophilic triterpene acids, which do not occur in conventional mistletoe preparations, were solubilised with β-cyclodextrins. The combination of an aqueous extract (viscum) and a triterpene-containing extract (TT) recreated a whole mistletoe extract (viscumTT). These extracts were tested on rhabdomyosarcoma in vitro, ex vivo, and in vivo with regard to anticancer effects. Viscum and viscumTT inhibited cell proliferation and induced apoptosis effectively in a dose-dependent manner in vitro and ex vivo, whereas TT showed only moderate inhibitory effects. viscumTT proved to be more effective than the single extracts and displayed a synergistic effect in vitro and a stronger effect in vivo. viscumTT induced apoptosis via the extrinsic and intrinsic pathways, evidenced by the loss of mitochondrial membrane potential and activation of CASP8 and CASP9. CASP10 inhibitor inhibited apoptosis effectively, emphasising the importance of CASP10 in viscumTT-induced apoptosis. Additionally, viscumTT changed the ratio of apoptosis-associated proteins by downregulation of antiapoptotic proteins such as XIAP and BIRC5, thus shifting the balance towards apoptosis. viscumTT effectively reduced tumour volume in patient-derived xenografts in vivo and may be considered a promising substance for rhabdomyosarcoma therapy. |
| format | Article |
| id | doaj-art-30694753a35a4838af57be60e68f95ee |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-30694753a35a4838af57be60e68f95ee2025-02-03T05:43:44ZengWileyJournal of Immunology Research2314-88612314-71562017-01-01201710.1155/2017/48742804874280Synergistic Antitumour Properties of viscumTT in Alveolar RhabdomyosarcomaRahel Mascha Stammer0Susann Kleinsimon1Jana Rolff2Sebastian Jäger3Angelika Eggert4Georg Seifert5Catharina I. Delebinski6Department of Paediatric Oncology/Haematology, Otto-Heubner Centre for Paediatric and Adolescent Medicine (OHC), Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, GermanyDepartment of Paediatric Oncology/Haematology, Otto-Heubner Centre for Paediatric and Adolescent Medicine (OHC), Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, GermanyEPO GmbH, Experimental Pharmacology & Oncology, Robert-Rössle-Str. 10, 13125 Berlin-Buch, GermanyBirken AG, Streiflingsweg 11, 75223 Niefern-Öschelbronn, GermanyDepartment of Paediatric Oncology/Haematology, Otto-Heubner Centre for Paediatric and Adolescent Medicine (OHC), Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, GermanyDepartment of Paediatric Oncology/Haematology, Otto-Heubner Centre for Paediatric and Adolescent Medicine (OHC), Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, GermanyDepartment of Paediatric Oncology/Haematology, Otto-Heubner Centre for Paediatric and Adolescent Medicine (OHC), Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, GermanyAqueous mistletoe extracts from the European mistletoe (Viscum album) contain mainly mistletoe lectins and viscotoxins as cytotoxic compounds. Lipophilic triterpene acids, which do not occur in conventional mistletoe preparations, were solubilised with β-cyclodextrins. The combination of an aqueous extract (viscum) and a triterpene-containing extract (TT) recreated a whole mistletoe extract (viscumTT). These extracts were tested on rhabdomyosarcoma in vitro, ex vivo, and in vivo with regard to anticancer effects. Viscum and viscumTT inhibited cell proliferation and induced apoptosis effectively in a dose-dependent manner in vitro and ex vivo, whereas TT showed only moderate inhibitory effects. viscumTT proved to be more effective than the single extracts and displayed a synergistic effect in vitro and a stronger effect in vivo. viscumTT induced apoptosis via the extrinsic and intrinsic pathways, evidenced by the loss of mitochondrial membrane potential and activation of CASP8 and CASP9. CASP10 inhibitor inhibited apoptosis effectively, emphasising the importance of CASP10 in viscumTT-induced apoptosis. Additionally, viscumTT changed the ratio of apoptosis-associated proteins by downregulation of antiapoptotic proteins such as XIAP and BIRC5, thus shifting the balance towards apoptosis. viscumTT effectively reduced tumour volume in patient-derived xenografts in vivo and may be considered a promising substance for rhabdomyosarcoma therapy.http://dx.doi.org/10.1155/2017/4874280 |
| spellingShingle | Rahel Mascha Stammer Susann Kleinsimon Jana Rolff Sebastian Jäger Angelika Eggert Georg Seifert Catharina I. Delebinski Synergistic Antitumour Properties of viscumTT in Alveolar Rhabdomyosarcoma Journal of Immunology Research |
| title | Synergistic Antitumour Properties of viscumTT in Alveolar Rhabdomyosarcoma |
| title_full | Synergistic Antitumour Properties of viscumTT in Alveolar Rhabdomyosarcoma |
| title_fullStr | Synergistic Antitumour Properties of viscumTT in Alveolar Rhabdomyosarcoma |
| title_full_unstemmed | Synergistic Antitumour Properties of viscumTT in Alveolar Rhabdomyosarcoma |
| title_short | Synergistic Antitumour Properties of viscumTT in Alveolar Rhabdomyosarcoma |
| title_sort | synergistic antitumour properties of viscumtt in alveolar rhabdomyosarcoma |
| url | http://dx.doi.org/10.1155/2017/4874280 |
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