Chapter 12 - Saponins Produced by Gypsophila Species Enhance the Toxicity of Type I Ribosome-Inactivating Proteins

Abstract

Abstract Saponins are a widespread class of natural compounds found in a lot of plant species. Saponins in general are surface active compounds which give stable foams in water and were shown to effect the plasma membrane of living cells and model membranes by interacting with cholesterol. They are mainly produced by plants and of lower molecular weight (2 kDa). Analysis of saponin compounds, however, can be quite compelling due to such factors as their complexity, amphiphilic structure, lack of strong chromophore, and prone to form unsoluble aggregates in solution which can make purification and quantitation difficult. Underground parts from Gypsophila species (Caryophyllaceae) are an especially rich source of triterpenoid saponins. They are exploited commercially for a variety of purposes including medicines, detergents, adjuvants, and cosmetics. The most common basic structure of sapogenins isolated from Gypsophila genus is mainly gypsogenin but also in fewer amounts gypsogenic acid and quillaic acid. Also, it is shown that aldehyde group at C-4 of sapogenins from Gypsophila is related to cytotoxic activity against human cancer cell lines. Recently, it was shown that Gypsophila saponins amplify the toxicity of saporin and agrostin type I RIPs (ribosome-inactivating proteins) and RIP-based chimeric toxins (Hebestreit, 2006 [28] ). Currently, we showed that nebulosides A and B, novel triterpenoid saponins from Gypsophila arrostii var. nebulosa , a typically Turkish variety, significantly enhanced toxicity of saporin on ECV-304 cell lines. RIPs, generally unable to penetrate the cellular membrane, remove specific adenine residues from the 28S rRNA as part of process that leads to inhibition of protein synthesis. This situation is not based on the damage of cellular membranes by the Gypsophila saponins. Currently, it is known that Gypsophila saponins trigger clathrin-mediated endocytosis of RIPs. This brings up a strong enhancement of toxicity for the naturally membrane-impermeable type I RIPs, making them as toxic as the membrane-permeable type II RIPs, like viscumin and ricin at the same concentration.