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槲寄生植物提取物在体内外诱导急性淋巴细胞白血病细胞凋亡的分子机制

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

作者信息

Seifert Georg, Jesse Patrick, Laengler Alfred, Reindl Tobias, Lüth Maria, Lobitz Stephan, Henze Günter, Prokop Aram, Lode Holger N

机构信息

Department of Pediatric Oncology/Hematology, Otto-Heubner-Center for Pediatric and Adolescent Medicine, Charité, Universitätsmedizin Berlin, Germany.

出版信息

Cancer Lett. 2008 Jun 18;264(2):218-28. doi: 10.1016/j.canlet.2008.01.036. Epub 2008 Mar 7.

DOI:10.1016/j.canlet.2008.01.036
PMID:18314258
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.

摘要

欧洲槲寄生是应用最为广泛的替代癌症疗法之一。槲寄生水提取物(MT)含有三种槲寄生凝集素I、II和III,是一类主要的生物活性剂。尽管MT被广泛应用,但缺乏科学可靠的临床前和临床数据。在本文中,我们首次描述了MT在淋巴细胞白血病中的体内疗效及作用机制。为此,我们首先研究了两种标准化槲寄生水提取物(从冷杉中提取的MT(MT-A);从松树中提取的MT(MT-P))对人急性淋巴细胞白血病(ALL)细胞系(NALM-6)的细胞毒性作用及其作用机制。通过Casy Count分析确定,MT-A、MT-P和ML-I在极低浓度下即可抑制细胞增殖,其中MT-P是细胞毒性最强的提取物。DNA片段化分析表明,剂量依赖性诱导凋亡是细胞死亡的主要机制。最后,我们在B系前体ALL(NALM-6)的体内SCID模型中评估了MT-A和MT-P的疗效。与对照组(34.6天)相比,两种MT在所有测试浓度下均显著提高了生存率(高达55.4天),且无副作用。

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