Saponinum album, a mixture of triterpenoic saponins derived from Gypsophila species, led to an increased internalization of agrostin, a ribosome-inactivating-protein (RIP) type I in U-937 cells differentiated with interferon-gamma or phorbol myristate acetate. Treatment with agrostin only showed no cytotoxicity. It was hypothesized that saponinum album stimulated phagocytosis and by that the uptake of agrostin. For this purpose phagocytosis experiments with Alexa-Fluor-488-labelled 1-microm amino-latex beads and FITC-labelled Escherichia coli (K-12 strain) were performed. The results indicated no stimulation of phagocytosis by treatment with saponinum album.
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http://dx.doi.org/10.1211/jpp.60.7.0015 | DOI Listing |
Int J Mol Sci
November 2020
The Simon Flavell Leukaemia Research Laboratory, Southampton General Hospital, Southampton SO16 6YD, UK.
Cholesterol seems to play a central role in the augmentation of saporin-based immunotoxin (IT) cytotoxicity by triterpenoid saponins. Endolysosomal escape has been proposed as one mechanism for the saponin-mediated enhancement of targeted toxins. We investigated the effects of lipid depletion followed by repletion on (SA)-induced endolysosomal escape of Alexa Fluor labelled saporin and the saporin-based immunotoxin OKT10-SAP, directed against CD38, in Daudi lymphoma cells.
View Article and Find Full Text PDFToxins (Basel)
February 2019
The Simon Flavell Leukaemia Research Laboratory, Southampton General Hospital, Southampton SO16 6YD, UK.
Triterpenoid saponins from (SA) significantly augment the cytotoxicity of saporin-based immunotoxins but the mechanism of augmentation is not fully understood. We investigated the effects of six small molecule pharmacological agents, which interfere with endocytic and other processes, on SA-mediated augmentation of saporin and saporin-based immunotoxins (ITs) directed against CD7, CD19, CD22 and CD38 on human lymphoma and leukaemia cell lines. Inhibition of clathrin-mediated endocytosis or endosomal acidification abolished the SA augmentation of saporin and of all four immunotoxins tested but the cytotoxicity of each IT or saporin alone was largely unaffected.
View Article and Find Full Text PDFBiochim Biophys Acta Biomembr
May 2017
The Simon Flavell Leukaemia Research Laboratory, Southampton General Hospital, Southampton, Hampshire SO16 6YD, United Kingdom. Electronic address:
Triterpenoid saponins from Saponinum Album (SA) exert potent lytic effects on eukaryotic cell plasma membranes and, when used at sub-lytic concentrations, significantly augment the cytotoxicity of saporin-based immunotoxins (IT). To help elucidate the mechanism(s) behind these two phenomena we investigated the role of cholesterol to both. Human Daudi lymphoma cells were lipid deprived using a combination of three different approaches.
View Article and Find Full Text PDFImmunopharmacol Immunotoxicol
February 2015
The Simon Flavell Leukaemia Research Laboratory, Southampton General Hospital, Southampton , UK .
Context: Saponinum album (SA) is a complex mixture of triterpenoid saponins previously shown to augment the cytotoxicity of the type I ribosome-inactivating protein saporin and an EGF-saporin target toxin that could potentially be used to improve the therapeutic window of targeted toxins.
Objective: To investigate the augmentative property of SA on saporin and saporin-based immunotoxins (IT) directed against five different cell surface target molecules on human leukemia and lymphoma cells.
Materials And Methods: After determining the optimum dose of SA for each cell line, the extent of SA-mediated augmentation was established for saporin and five saporin-based ITs using XTT and an annexin V apoptosis assay.
Pharmazie
October 2011
Institut für Laboratoriumsmedizin, Klinische Chemie und Pathobiochemie, Charité - Universitätsmedizin, Berlin, Germany.
Saponinum album (Merck) is a complex composite of triterpene saponins. It was shown that Saponinum album (Merck) dramatically enhances the toxicity of the N-glycosylase saporin from the seeds of Saponaria officinalis L. as well as the toxicity of a saporin based anti-tumor toxin.
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