Abstract |
Saponins are amphiphilic secondary plant compounds able to interfere with surfaces and permeabilize membranes. In addition to antimicrobial and anti-inflammatory features, anti-neoplastic activities are described which base on various mechanisms. A very promising anti- cancer strategy is the synergistic enhancement of the cytotoxicity of ribosome-inactivating proteins type I (RIP-I) by suitable saponins. The cytotoxicity of the naturally low cytotoxic activity showing RIP-I can be augmented up to 100,000-fold, if they are applied in combination with appropriate saponins. These saponins have to hold certain structural features. We analyzed 56 different saponins for their non-synergistic, as well as their synergistic cytotoxicity with the RIP-I saporin from Saponaria officinalis L. (Caryophyllaceae). The saponins were assorted into categories, according to their structural features and their cytotoxic behavior, to build up structure-activity relationships. A non-synergistic cytotoxicity as low as possible and a synergistic cytotoxicity as high as possible were desired. The investigations suggest that ideal saponins consist of an oleanane-type scaffold, preferably gypsogenin or quillaic acid, three branched sugars at the C-3-OH-group including glucuronic acid, galactose, xylose and four branched sugars at the C-28-OH-group, including deoxy-sugars and acetyl-residues.
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Authors | Stefan Böttger, Elena Westhof, Karsten Siems, Matthias F Melzig |
Journal | Toxicon : official journal of the International Society on Toxinology
(Toxicon)
Vol. 73
Pg. 144-50
(Oct 2013)
ISSN: 1879-3150 [Electronic] England |
PMID | 23891686
(Publication Type: Journal Article)
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Copyright | Copyright © 2013 Elsevier Ltd. All rights reserved. |
Chemical References |
- Ribosome Inactivating Proteins, Type 1
- Saponins
- Tetrazolium Salts
- Thiazoles
- thiazolyl blue
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Topics |
- Cell Line, Tumor
- Colorimetry
- Epithelial Cells
(metabolism)
- Fluorescence
- Humans
- Inhibitory Concentration 50
- Models, Molecular
- Molecular Structure
- Ribosome Inactivating Proteins, Type 1
(metabolism, toxicity)
- Saponins
(chemistry, metabolism)
- Structure-Activity Relationship
- Tetrazolium Salts
- Thiazoles
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