Viscumins functionally modulate cell motility-associated gene expression

Schötterl,Sonja; Hübner,Miriam; Armento,Angela; Veninga,Vivien; Wirsik,Naita Maren; Bernatz,Simon; Lentzen,Hans; Mittelbronn,Michel; Naumann,Ulrike

doi:10.3892/ijo.2017.3838

Viscumins functionally modulate cell motility-associated gene expression

Authors:
- Sonja Schötterl
- Miriam Hübner
- Angela Armento
- Vivien Veninga
- Naita Maren Wirsik
- Simon Bernatz
- Hans Lentzen
- Michel Mittelbronn
- Ulrike Naumann
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Affiliations: 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, Melema Pharma GmbH, D-20148 Hamburg, Germany
Published online on: January 3, 2017 https://doi.org/10.3892/ijo.2017.3838
Pages: 684-696

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Abstract

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.

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