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Different studies describe the anti-inflammatory effects of Scrophulariaspecies, a medicinal plant widely used in folk medicine since ancient times. Asknowledge regarding the anti-neoplastic properties of this species is rather limited,we investigated the influence of methanol extracts of different Scrophularia specieson cell proliferation, cell death, and tumour cell intravasation through the lymphendothelial barrier. HL-60 leukaemia cells were treated with methanol extractsof different Scrophularia species leading to strong growth inhibition and highcell death rates. The expression of cell cycle regulators, oncogenes and celldeath inducers was determined by Western blot analysis. Furthermore the effectof 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 monolayersthat were induced by MCF-7 breast cancer spheroids. Methanol extracts of Scrophulariaspecies exhibited strong anti-proliferative properties. S. floribunda extractinhibited G2/M- and later on S-phase and S. lucida inhibited S-phase and in bothcases this was associated with the down-regulation of c-Myc expression. Extractsof S. floribunda and S. lucida led to necrosis and apoptosis, respectively. Furthermore,S. lucida, but not S. floribunda, effectively attenuated tumour cell intravasationthrough lymph endothelial cell monolayers, which correlated with the inhibitionof NF-κB. S. lucida exhibited promising anti-neoplastic effects and this was mostlikely due to the down-regulation of various cell cycle regulators, proto-oncogenesand NF-κB and the activation of caspase-3.

Effects of Scrophularia extracts on tumor cell proliferation, death and intravasation through lymphoendothelial cell barriers