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Saponins from Saponaria officinalis L. Augment the Efficacy of a Rituximab-Immunotoxin
- Source :
- Planta Medica. 82:1525-1531
- Publication Year :
- 2016
- Publisher :
- Georg Thieme Verlag KG, 2016.
-
Abstract
- Triterpenoidal saponins are synthesized in the roots of Saponaria officinalis L. 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 its N-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 GI50 of 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 from S. officinalis L. is therefore a new strategy to potentially improve the cytotoxicity and therapeutic efficacy of Rituximab-immunotoxins for the treatment of B-cell lymphoma.
- Subjects :
- Lymphoma, B-Cell
Saporin
Cell Survival
Saponin
Pharmaceutical Science
02 engineering and technology
Pharmacology
complex mixtures
Cell Line
Analytical Chemistry
03 medical and health sciences
0302 clinical medicine
Saponaria
Immunotoxin
parasitic diseases
Drug Discovery
Humans
Saponaria officinalis
Receptor
Cytotoxicity
Chromatography, High Pressure Liquid
chemistry.chemical_classification
biology
Immunotoxins
Organic Chemistry
Drug Synergism
Saponins
021001 nanoscience & nanotechnology
biology.organism_classification
Saporins
carbohydrates (lipids)
Complementary and alternative medicine
chemistry
Cell culture
030220 oncology & carcinogenesis
Immunology
Ribosome Inactivating Proteins, Type 1
biology.protein
Molecular Medicine
Rituximab
0210 nano-technology
Subjects
Details
- ISSN :
- 14390221 and 00320943
- Volume :
- 82
- Database :
- OpenAIRE
- Journal :
- Planta Medica
- Accession number :
- edsair.doi.dedup.....4cb6ae24e0d5b2b044b5e3aeccb457bb