Molecular mechanisms of mistletoe plant extract-induced apoptosis in acute lymphoblastic leukemia in vivo and in vitro.
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.
Seifert
Georg
G
Department of Pediatric Oncology/Hematology, Otto-Heubner-Center for Pediatric and Adolescent Medicine, Charité, Universitätsmedizin Berlin, Germany. georg.seifert@charite.de
Jesse
Patrick
P
Laengler
Alfred
A
Reindl
Tobias
T
Lüth
Maria
M
Lobitz
Stephan
S
Henze
Günter
G
Prokop
Aram
A
Lode
Holger N
HN
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D016513:Mice, SCID; D014784:Mistletoe / Q000737:chemistry*; D008517:Phytotherapy; D010936:Plant Extracts / Q000627:therapeutic use*; D037121:Plant Lectins / Q000627:therapeutic use; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D010936:Plant Extracts; D037121:Plant Lectins