title: Saponins from Saponaria officinalis L. Augment the Efficacy of a Rituximab-Immunotoxin.
abstract: Triterpenoidal saponins are synthesized in the roots ofSaponaria officinalisL. The same plant is also a source for the toxin Saporin, which is a ribosome-inactivating protein. Triterpenoidal saponins are known to increase the cytotoxicity of Saporin by modulating its intracellular trafficking. Here, we investigated if the combinatorial effects elicited by purified saponins and Saporin can be applied to increase the therapeutic efficacy of the immunotoxin Saporin-Rituximab. First, saponins were purified by high-performance liquid chromatography. Thereafter, their intrinsic cytotoxicity was evaluated on Ramos cells with no observed effect up to 5 µg/mL, however, saponins increased the cytotoxicity of Saporin, while no influence was observed on itsN-glycosidase activity. Saporin-Rituximab bound to CD20 in Ramos cells and, in the absence of saponins, had a GI50(concentration inhibiting cell growth to 50 %) of 7 nM. However, in the presence of a nontoxic concentration of saponins, the GI50of Saporin-Rituximab was 0.01 nM, a nearly 700-fold increase in efficacy. Moreover, two further immunotoxins, namely Saporin-anti-CD22 and Saporin-anti-CD25, were tested in combination with saponins yielding enhancement factors of 170-fold and 25-fold, respectively. All three receptors are present in Ramos cells and the differences in cytotoxicity enhancement may be explained by the differing expression levels of the cellular receptors. The application of purified saponins fromS. officinalisL. is therefore a new strategy to potentially improve the cytotoxicity and therapeutic efficacy of Rituximab-immunotoxins for the treatment of B-cell lymphoma.
authors.affiliation: Institut für Laboratoriumsmedizin, Klinische Chemie und Pathobiochemie, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany.
authors.forename: Roger
authors.initials: R
authors.lastname: Gilabert-Oriol
authors.affiliation: Institut für Laboratoriumsmedizin, Klinische Chemie und Pathobiochemie, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany.
authors.forename: Mayank
authors.initials: M
authors.lastname: Thakur
authors.affiliation: Institut für Laboratoriumsmedizin, Klinische Chemie und Pathobiochemie, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany.
authors.forename: Katy
authors.initials: K
authors.lastname: Haussmann
authors.affiliation: Institut für Laboratoriumsmedizin, Klinische Chemie und Pathobiochemie, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Niesler
authors.affiliation: Institut für Laboratoriumsmedizin, Klinische Chemie und Pathobiochemie, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany.
authors.forename: Cheenu
authors.initials: C
authors.lastname: Bhargava
authors.affiliation: Institut für Pharmazie, Freie Universität Berlin, Berlin, Germany.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Görick
authors.affiliation: Institut für Laboratoriumsmedizin, Klinische Chemie und Pathobiochemie, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Fuchs
authors.affiliation: Institut für Pharmazie, Freie Universität Berlin, Berlin, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Weng
mesh_terms: D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004357:Drug Synergism; D006801:Humans; D000922:Immunotoxins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D016393:Lymphoma, B-Cell / Q000473:pathology*; D054789:Ribosome Inactivating Proteins, Type 1 / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000069283:Rituximab / Q000494:pharmacology*; D029750:Saponaria / Q000737:chemistry*; D012503:Saponins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000076985:Saporins
chemical_list: D000922:Immunotoxins; D054789:Ribosome Inactivating Proteins, Type 1; D012503:Saponins; D000069283:Rituximab; D000076985:Saporins