title: Viscumins functionally modulate cell motility-associated gene expression.
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.
authors.affiliation: Molecular Neuro-Oncology, Hertie Institute for Clinical Brain Research and Center Neurology, University of Tübingen, D-72076 Tübingen, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Schötterl
authors.affiliation: Molecular Neuro-Oncology, Hertie Institute for Clinical Brain Research and Center Neurology, University of Tübingen, D-72076 Tübingen, Germany.
authors.forename: Miriam
authors.initials: M
authors.lastname: Hübner
authors.affiliation: Molecular Neuro-Oncology, Hertie Institute for Clinical Brain Research and Center Neurology, University of Tübingen, D-72076 Tübingen, Germany.
authors.forename: Angela
authors.initials: A
authors.lastname: Armento
authors.affiliation: Molecular Neuro-Oncology, Hertie Institute for Clinical Brain Research and Center Neurology, University of Tübingen, D-72076 Tübingen, Germany.
authors.forename: Vivien
authors.initials: V
authors.lastname: Veninga
authors.affiliation: Edinger Institute (Neurological Institute), Goethe University, D-60528 Frankfurt/Main, Germany.
authors.forename: Naita Maren
authors.initials: NM
authors.lastname: Wirsik
authors.affiliation: Edinger Institute (Neurological Institute), Goethe University, D-60528 Frankfurt/Main, Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Bernatz
authors.affiliation: Melema Pharma GmbH, D-20148 Hamburg, Germany.
authors.forename: Hans
authors.initials: H
authors.lastname: Lentzen
authors.affiliation: Edinger Institute (Neurological Institute), Goethe University, D-60528 Frankfurt/Main, Germany.
authors.forename: Michel
authors.initials: M
authors.lastname: Mittelbronn
authors.affiliation: Molecular Neuro-Oncology, Hertie Institute for Clinical Brain Research and Center Neurology, University of Tübingen, D-72076 Tübingen, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Naumann
mesh_terms: D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005909:Glioblastoma / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D009361:Neoplasm Invasiveness; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010936:Plant Extracts / Q000494:pharmacology; D054790:Ribosome Inactivating Proteins, Type 2 / Q000494:pharmacology*; D015398:Signal Transduction; D014118:Toxins, Biological / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000235:genetics*; D028182:Viscum album / Q000737:chemistry
chemical_list: D010936:Plant Extracts; D054790:Ribosome Inactivating Proteins, Type 2; D014118:Toxins, Biological; D016212:Transforming Growth Factor beta; C488862:mistletoe lectin I