Molecular mechanisms of mistletoe plant extract-induced apoptosis in acute lymphoblastic leukemia in vivo and in vitro

Abstract Viscum album (Mistletoe) is one of the most widely used alternative cancer therapies. Aqueous mistletoe extracts (MT) contain the three mistletoe lectins I, II and III as one predominant group of biologically active agents. Although MT is widely used, there is a lack of scientifically sound...

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Bibliographic Details
Published in:Cancer letters 2008-06, Vol.264 (2), p.218-228
Main Authors: Seifert, Georg, Jesse, Patrick, Laengler, Alfred, Reindl, Tobias, Lüth, Maria, Lobitz, Stephan, Henze, Günter, Prokop, Aram, Lode, Holger N
Format: Article
Language:English
Subjects:
ALL
Alternative
Animals
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Apoptosis
Apoptosis - drug effects
Cell Line, Tumor
Cell Proliferation - drug effects
Cytotoxicity
Experiments
Helixor
Hematology, Oncology and Palliative Medicine
Humans
In Vitro Techniques
Lectins
Leukemia
Male
Membrane Potential, Mitochondrial - drug effects
Mice
Mice, SCID
Mistletoe
Mistletoe - chemistry
Molecular weight
NALM-6
Phytotherapy
Plant Extracts - therapeutic use
Plant Lectins - therapeutic use
Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy
Proteins
Santalales
SCID
Studies
Test systems
Toxicity
Viscum album
Xenograft Model Antitumor Assays
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Summary:Abstract Viscum album (Mistletoe) is one of the most widely used alternative cancer therapies. Aqueous mistletoe extracts (MT) contain the three mistletoe lectins I, II and III as one predominant group of biologically active agents. Although MT is widely used, there is a lack of scientifically sound preclinical and clinical data. In this paper, we describe for the first time the in vivo efficacy and mechanism of action of MT in lymphoblastic leukemia. For this purpose, we first investigated both the cytotoxic effect and the mechanism of action of two standardized aqueous MTs (MT obtained from fir trees (MT-A); MT obtained from pine trees (MT-P)) in a human acute lymphoblastic leukemia (ALL) cell line (NALM-6). MT-A, MT-P and ML-I inhibited cell proliferation as determined by Casy® Count analysis at very low concentrations with MT-P being the most cytotoxic extract. DNA-fragmentation assays indicated that dose-dependent induction of apoptosis was the main mechanism of cell death. Finally, we evaluated the efficacy of MT-A and MT-P in an in vivo SCID-model of pre-B ALL (NALM-6). Both MTs significantly improved survival (up to 55.4 days) at all tested concentrations in contrast to controls (34.6 days) without side effects.
ISSN:0304-3835
1872-7980
DOI:10.1016/j.canlet.2008.01.036