Saponins as Tool for Improved Targeted Tumor Therapies

Abstract

Saponins are plant glycosides that consist of a steroid, steroid alkaloid or triterpenoid aglycone and one or more sugar chains that are covalently linked by glycosidic binding to the aglycone. Glucose, galactose, glucuronic acid, xylose and rhamnose are commonly bound monosaccharides. Saponins are found in all organs of a variety of higher plants. Due to the great variability of their structures, diverse functions have been described for distinct saponins; including foaming and pore forming properties as well as selective removal of protozoa from the rumen. The most interesting properties are, however, favorable anti-tumorigenic effects. Several saponins inhibit tumor cell growth by cell cycle arrest and apoptosis with half maximal inhibitory concentrations of down to 0.2 microM. A drawback of saponins in tumor therapy is the non-targeted spreading throughout the whole body. Surprisingly, certain saponins were identified that drastically enhance the efficacy of targeted chimeric toxins bearing the ribosome-inactivating protein saporin as cell-killing moiety. It was demonstrated that this effect is substantially more pronounced on target cells than on non-target cells, thus not only preserving the target specificity of the chimeric toxin but also broadening the therapeutic window with simultaneous dose lowering. This review describes the role of saponins as drug in general, their use as single drug treatment in tumor therapy, their combination with conventional tumor treatment strategies and the synergistic effects with particular targeted tumor therapies that are based on recombinant proteins.

Glycosylated Triterpenoids as Endosomal Escape Enhancers in Targeted Tumor Therapies

“…Particular glycosylated triterpenes were found to act as tremendous endosomal escape enhancers for targeted toxins in tumor therapy [17,18,19]. These toxins essentially comprise ribosome-inactivating proteins (RIPs), a class of toxic plant enzymes that release a specific adenine residue from ribosomal RNA finally resulting in the arrest of protein synthesis and apoptosis [20].…”

Cytotoxicity of the saponin TTB2 on Ewing sarcoma cells

“…Previous studies have elucidated that the biological and pharmacological properties of saponins are associated with their structural diversity. These are exploited in a number of traditional and industrial applications (11,12). TTB2 is one of the steroidal saponins isolated from T. tschonoskii Maxim (9); its pharmacological effects and mechanisms remain unclear.…”

Barbarea vulgaris linkage map and quantitative trait loci for saponins, glucosinolates, hairiness and resistance to the herbivore Phyllotreta nemorum

“…Due to the large variability in structure, various functions have been described for different saponins, including their role as defense compounds against pathogens and herbivores (reviewed in Sparg et al, 2004). They are also constituents of many plant drugs and folk medicines, as they exert pharmacological effects including anti-tumorigenic, antiinflammatory and immunomodulatory effects (reviewed in Fuchs et al, 2009;Hostettmann and Marston, 1995;Sultana and Ata, 2008;Sun et al, 2009). While glucosinolates are prevalent in crucifers, B. vulgaris is the only crucifer known to accumulate saponins.…”