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

被引:94
作者
Seifert, Georg [1 ]
Jesse, Patrick [1 ]
Laengler, Alfred [3 ]
Reindl, Tobias [1 ]
Lueth, Maria [1 ]
Lobitz, Stephan [1 ]
Henze, Guenter [1 ]
Prokop, Aram [1 ]
Lode, Holger N. [2 ]
机构
[1] Charite, Otto Heubner Ctr Kinder & Jugend Med, Klin Padiat Mit Schwerpunkt Onkol Hamatol, Dept Pediat Oncol Hematol, D-13353 Berlin, Germany
[2] Charite, Otto Heubner Ctr Kinder & Jugend Med, Dept Pediat & BMT, D-13353 Berlin, Germany
[3] Gemeinschaftskrankenhaus, Dept Paediat, Herdecke, Germany
关键词
mistletoe; ALL; leukemia; apoptosis; SCID; NALM-6; Helixor; alternative; phytotherapy;
D O I
10.1016/j.canlet.2008.01.036
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
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 NIT 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 NIT in lymphoblastic leukemia. For this purpose.. we first investigated both the cytotoxic effect and the mechanism of action of two standardized aqueous MTs (NIT 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(R) 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. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:218 / 228
页数:11
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