title: Effects of Scrophularia extracts on tumor cell proliferation, death             and intravasation through lymphoendothelial cell barriers.
abstract: Different studies describe the anti-inflammatory effects of Scrophularia             species, a medicinal plant widely used in folk medicine since ancient times. As             knowledge regarding the anti-neoplastic properties of this species is rather limited,             we investigated the influence of methanol extracts of different Scrophularia species             on cell proliferation, cell death, and tumour cell intravasation through the lymph             endothelial barrier. HL-60 leukaemia cells were treated with methanol extracts             of different Scrophularia species leading to strong growth inhibition and high             cell death rates. The expression of cell cycle regulators, oncogenes and cell             death inducers was determined by Western blot analysis. Furthermore the effect             of S. lucida was studied in an NF-κB reporter assay, and in a novel assay measuring             'circular chemo-repellent-induced defects' (CCID) in lymph endothelial monolayers             that were induced by MCF-7 breast cancer spheroids. Methanol extracts of Scrophularia             species exhibited strong anti-proliferative properties. S. floribunda extract             inhibited G2/M- and later on S-phase and S. lucida inhibited S-phase and in both             cases this was associated with the down-regulation of c-Myc expression. Extracts             of S. floribunda and S. lucida led to necrosis and apoptosis, respectively. Furthermore,             S. lucida, but not S. floribunda, effectively attenuated tumour cell intravasation             through lymph endothelial cell monolayers, which correlated with the inhibition             of NF-κB. S. lucida exhibited promising anti-neoplastic effects and this was most             likely due to the down-regulation of various cell cycle regulators, proto-oncogenes             and NF-κB and the activation of caspase-3.
authors.affiliation: Institute of Clinical Pathology, Medical University of Vienna,                     A-1090 Vienna, Austria.
authors.forename: Benedikt
authors.initials: B
authors.lastname: Giessrigl
authors.forename: Gökhan
authors.initials: G
authors.lastname: Yazici
authors.forename: Mathias
authors.initials: M
authors.lastname: Teichmann
authors.forename: Sabine
authors.initials: S
authors.lastname: Kopf
authors.forename: Sara
authors.initials: S
authors.lastname: Ghassemi
authors.forename: Atanas G
authors.initials: AG
authors.lastname: Atanasov
authors.forename: Verena M
authors.initials: VM
authors.lastname: Dirsch
authors.forename: Michael
authors.initials: M
authors.lastname: Grusch
authors.forename: Walter
authors.initials: W
authors.lastname: Jäger
authors.forename: Ali
authors.initials: A
authors.lastname: Ozmen
authors.forename: Georg
authors.initials: G
authors.lastname: Krupitza
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology*; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D018920:Coculture Techniques; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D008207:Lymphatic Metastasis; D020935:MAP Kinase Signaling System; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009857:Oncogenes; D010936:Plant Extracts / Q000494:pharmacology*; D010946:Plants, Medicinal / Q000737:chemistry*; D032266:Scrophularia / Q000737:chemistry*; D018874:Spheroids, Cellular / Q000187:drug effects
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D018797:Cell Cycle Proteins; D016328:NF-kappa B; D010936:Plant Extracts; C505407:CASP3 protein, human; D053148:Caspase 3