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

Abstract

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 downregulation of various cell cycle regulators, proto-oncogenes and NF-κB and the activation of caspase-3.

The Acetone Extract ofSclerocarya birrea(Anacardiaceae) Possesses Antiproliferative and Apoptotic Potential against Human Breast Cancer Cell Lines (MCF-7)

“…Apoptotic-morphological features have been reported in various studies involving plants and anticancer agents on cancer lines [4, 18, 21]. In our current study, morphological modifications were clearly visible during apoptosis.…”

“…Plant-based research has been paramount in the discovery of biological active compounds, and derivatives from plant have been found with anticancer properties [2, 4, 18, 23]. Previous studies conducted indicated profound activity of the acetone extract of S. birrea against different microorganisms including H. pylori which has been incriminated in gastric carcinoma [13, 20].…”

“…Various investigators have conducted studies on different plants employing both in vivo and in vitro approaches to evaluate their anticancer potential following an intensive quest for anticancer agents from plants and other natural sources [15–18]. Research on S. birrea has been extensive but largely on their antimicrobial, antiprotozoal, and antioxidant activities of which the plant and associated extracts have proven its potential.…”

NF-κB Inhibitors from Eurycoma longifolia

“…14 In order to investigate a potential NF-κB inhibition, HEK-293/NF-κB-luc cells were used, which is a stable cell line containing an NF-κB-driven luciferase reporter gene that was successfully applied previously for activity profiling of a variety of medicinal plant extracts. 15−18 The methanol extract of the roots of E. longifolia revealed promising NF-κB inhibitory effects (66.9 ± 3.2%) at a concentration of 10 μg/mL. Therefore, a bioguided isolation procedure was conducted to identify the active principle(s), which led to the isolation of 28 compounds including a new quassinoid ( 1 ).…”

In vitro inhibition of breast cancer spheroid-induced lymphendothelial defects resembling intravasation into the lymphatic vasculature by acetohexamide, isoxsuprine, nifedipin and proadifen

“…One hour after treatment, cells were stimulated with 2 ng ml −1 human recombinant TNF α for additional 4 h. Luminescence of the firefly luciferase and fluorescence of the GFP were quantified on a GeniusPro plate reader (Tecan, Grödig, Austria). The luciferase signal derived from the NF- κ B reporter was normalised by the GFP-derived fluorescence to account for differences in cell number (Giessrigl et al , 2012). …”