Schötterl Sonja, Hübner Miriam, Armento Angela, Veninga Vivien, Wirsik Naita Maren, Bernatz Simon, Lentzen Hans, Mittelbronn Michel, Naumann Ulrike
Molecular Neuro-Oncology, Hertie Institute for Clinical Brain Research and Center Neurology, University of Tübingen, D-72076 Tübingen, Germany.
Edinger Institute (Neurological Institute), Goethe University, D-60528 Frankfurt/Main, Germany.
Int J Oncol. 2017 Feb;50(2):684-696. doi: 10.3892/ijo.2017.3838. Epub 2017 Jan 3.
In Europe extracts from Viscum album L., the European white-berry mistletoe, are widely used as a complementary cancer therapy. Viscumins (mistletoe lectins, ML) have been scrutinized as important active components of mistletoe and exhibit a variety of anticancer effects such as stimulation of the immune system, induction of cytotoxicity, reduction of tumor cell motility as well as changes in the expression of genes associated with cancer development and progression. By microarray expression analysis, quantitative RT-PCR and RT-PCR based validation of microarray data we demonstrate for the Viscum album extract Iscador Qu and for the lectins Aviscumine and ML-1 that in glioma cells these drugs differentially modulate the expression of genes involved in the regulation of cell migration and invasion, including processes modulating cell architecture and cell adhesion. A variety of differentially expressed genes in ML treated cells are associated with the transforming growth factor (TGF)-β signaling pathway or are targets of TGF-β. ML treatment downregulated the expression of TGF-β itself, of the TGF-β receptor II (TGFBR2), of the TGF-β intracellular signal transducer protein SMAD2, and of matrix-metalloproteinases (MMP) MMP-2 and MMP-14. Even if the changes in gene expression differ between Aviscumine, Iscador Qu and ML-1, the overall regulation of motility associated gene expression by all drugs showed functional effects since tumor cell motility was reduced in a ML-dependent manner. Therefore, ML containing compounds might provide clinical benefit as adjuvant therapeutics in the treatment of patients with invasively growing tumors such as glioblastomas.
在欧洲，欧洲白果槲寄生（Viscum album L.）的提取物被广泛用作癌症辅助治疗药物。槲寄生蛋白（槲寄生凝集素，ML）已被仔细研究为槲寄生的重要活性成分，并表现出多种抗癌作用，如刺激免疫系统、诱导细胞毒性、降低肿瘤细胞运动性以及改变与癌症发生和发展相关基因的表达。通过微阵列表达分析、定量逆转录聚合酶链反应（RT-PCR）以及基于RT-PCR对微阵列数据的验证，我们证明对于槲寄生提取物Iscador Qu以及凝集素Aviscumine和ML-1而言，在胶质瘤细胞中，这些药物可差异性地调节参与细胞迁移和侵袭调控的基因表达，包括调节细胞结构和细胞黏附的过程。ML处理的细胞中多种差异表达基因与转化生长因子（TGF）-β信号通路相关或为TGF-β的靶标。ML处理下调了TGF-β自身、TGF-β受体II（TGFBR2）、TGF-β细胞内信号转导蛋白SMAD2以及基质金属蛋白酶（MMP）MMP-2和MMP-14的表达。即使Aviscumine、Iscador Qu和ML-1之间基因表达的变化有所不同，但所有药物对运动相关基因表达的总体调节均显示出功能效应，因为肿瘤细胞运动性以ML依赖的方式降低。因此，含ML的化合物作为辅助治疗药物，可能对治疗侵袭性生长肿瘤（如胶质母细胞瘤）患者具有临床益处。
