title: A Natural Combination Extract of Viscum album L. Containing Both Triterpene Acids and Lectins Is Highly Effective against AML In Vivo.
abstract: Aqueous Viscum album L. extracts are widely used in complementary cancer medicine. Hydrophobic triterpene acids also possess anti-cancer properties, but due to their low solubility they do not occur in significant amounts in aqueous extracts. Using cyclodextrins we solubilised mistletoe triterpenes (mainly oleanolic acid) and investigated the effect of a mistletoe whole plant extract on human acute myeloid leukaemia cells in vitro, ex vivo and in vivo. Single Viscum album L. extracts containing only solubilised triterpene acids (TT) or lectins (viscum) inhibited cell proliferation and induced apoptosis in a dose-dependent manner in vitro and ex vivo. The combination of viscum and TT extracts (viscumTT) enhanced the induction of apoptosis synergistically. The experiments demonstrated that all three extracts are able to induce apoptosis via caspase-8 and -9 dependent pathways with down-regulation of members of the inhibitor of apoptosis and Bcl-2 families of proteins. Finally, the acute myeloid leukaemia mouse model experiment confirmed the therapeutic effectiveness of viscumTT-treatment resulting in significant tumour weight reduction, comparable to the effect in cytarabine-treated mice. These results suggest that the combination viscumTT may have a potential therapeutic value for the treatment AML.
authors.affiliation: Department of Paediatric Oncology/Haematology, Otto Heubner Centre for Paediatric and Adolescent Medicine (OHC), Charité -Universitaetsmedizin, Berlin, Germany.
authors.forename: Catharina I
authors.initials: CI
authors.lastname: Delebinski
authors.affiliation: Department of Paediatric Oncology/Haematology, Otto Heubner Centre for Paediatric and Adolescent Medicine (OHC), Charité -Universitaetsmedizin, Berlin, Germany.
authors.forename: Monika
authors.initials: M
authors.lastname: Twardziok
authors.affiliation: Department of Paediatric Oncology/Haematology, Otto Heubner Centre for Paediatric and Adolescent Medicine (OHC), Charité -Universitaetsmedizin, Berlin, Germany.
authors.forename: Susann
authors.initials: S
authors.lastname: Kleinsimon
authors.affiliation: Department of Cell Biology and Cell Pathology, Philipps University, Marburg, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Hoff
authors.affiliation: Institute of Pharmacy, Freie Universität, Berlin, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Mulsow
authors.affiliation: EPO GmbH, Berlin, Germany.
authors.forename: Jana
authors.initials: J
authors.lastname: Rolff
authors.affiliation: Birken AG, Niefern-Oeschelbronn, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Jäger
authors.affiliation: Department of Paediatric Oncology/Haematology, Otto Heubner Centre for Paediatric and Adolescent Medicine (OHC), Charité -Universitaetsmedizin, Berlin, Germany.
authors.forename: Angelika
authors.initials: A
authors.lastname: Eggert
authors.affiliation: Department of Paediatric Oncology/Haematology, Otto Heubner Centre for Paediatric and Adolescent Medicine (OHC), Charité -Universitaetsmedizin, Berlin, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Seifert
mesh_terms: D000293:Adolescent; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002648:Child; D004305:Dose-Response Relationship, Drug; D005260:Female; D018922:HL-60 Cells; D006801:Humans; D053631:Interleukin Receptor Common gamma Subunit / Q000172:deficiency / Q000235:genetics; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D009828:Oleanolic Acid / Q000008:administration & dosage / Q000494:pharmacology; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D037121:Plant Lectins / Q000008:administration & dosage / Q000494:pharmacology; D014315:Triterpenes / Q000008:administration & dosage / Q000494:pharmacology; D047368:Tumor Burden / Q000187:drug effects; D014407:Tumor Cells, Cultured; D020298:U937 Cells; D028182:Viscum album / Q000737:chemistry*; D023041:Xenograft Model Antitumor Assays
chemical_list: C507942:Il2rg protein, mouse; D053631:Interleukin Receptor Common gamma Subunit; D010936:Plant Extracts; D037121:Plant Lectins; D014315:Triterpenes; D009828:Oleanolic Acid