Therapeutic efficacy of natural compounds from Viscum album L. in acute lymphoblastic leukaemia.
Viscum album L. (mistletoe) is one of the most widely used complementary treatment in cancer therapy. However, due to their poor solubility, triterpenes, which are known to possess anticancer properties, are only present in aqueous extracts in negligible amounts. Using cyclodextrins it was possible to solubilise mistletoe triterpene acids (mainly oleanolic acid (OA)) and obtain a plant extract with high levels of OA and mistletoe lectins (ML). In the present study, we determined for the first time the efficacy of clearly defined mistletoe extracts against human acute lymphoblastic leukaemia (ALL) in vitro and in vivo. These mistletoe extracts contained either lectins (aqueous extract, viscum) or cyclodextrin solubilised triterpene acids (TT) such as oleanolic and betulinic acid and combinations thereof (viscumTT). We used the C.B-17/SCID mouse model of pre B ALL (NALM-6) and tested efficacy and mechanisms of treatment with these preparations in vitro and in vivo. Apoptosis was determined using mitochondrial potential, Annexin/PI assays and western blot analyses. Viscum album L extracts inhibited cell proliferation and showed cytotoxic properties in vitro. The Annexin/PI and mitochondrial potential assays indicated dose-dependent induction of apoptosis as the main mechanism of cell death. Based on these data, we investigated the effect of Viscum album L. extracts in vivo. Mice receiving PBS had a mean survival time of 38 days whereas viscumTT prolonged the mean survival to 50.5 days. In summary, we demonstrate for the first time that either solubilised triterpene acids or lectins and combinations thereof induce dose-dependent apoptosis in the ALL cell line NALM-6. Based on the in vivo data we believe that Viscum album L. extracts containing triterpene acids may possess impressive therapeutic potential. Thus, our investigations provide an important baseline for the design of further experimental studies and clinical trials to investigate the effects of individual compounds and potential synergisms in ALL.
Keywords: NALM-6; Mistletoe; ALL; Apoptosis; Phytotherapy; Oleanolic acid; Viscum album L.
Catharina I. Delebinski (a), Sebastian Jager (b), Kristin Kemnitz-Hassanin (a), Gunter Henze (a), Holger N. Lode (c), GeorgSeifert (a), *
(a) Department of Paediatric Oncology'/Haematology, Otto-Heubner-Centre for Paediatric and Adolescent Medicine (OHC), Charite, Universitdtsmedizin Berlin, Germany
(b) Betulin-lnstitute Darmstadt, Germany
(c) University of Greifswald, Department of Paediatric Haematology and Oncology, Greifswald, Germany
* Corresponding author. Tel.; +49 30 450 666 087; fax: +49 30 450 566 906.
E-mail address: firstname.lastname@example.org (G. Seifert).
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|Author:||Delebinski, Catharina I.; Jager, Sebastian; Kemnitz-Hassani, Kristin; Henze, Gunter; Lode, Holger N.|
|Publication:||Phytomedicine: International Journal of Phytotherapy & Phytopharmacology|
|Date:||Oct 15, 2011|
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