Targeted toxins and saponins – a powerful cooperation

Saponins from Gypsophila species are known to enhance the cytotoxicity of targeted toxins. In general targeted toxins consist of two components: a toxin moiety with enzymatic activity and a ligand moiety, which mediates specific binding to cancer cells. It was shown that saponins from Gypsophila paniculata L. enhanced the toxicity of a targeted toxin, composed of the N-glycosidase saporin from Saponaria officinalis L. and human epidermal growth factor up to 2,500 000-fold in primary breast cancer cells. Meanwhile the efficiency of the combined application of saponins and targeted toxins was shown in a mouse tumour model. Compared to the single application of the targeted toxin (SA2E), the combination with saponins lead to a tremendous reduction (at least 50-fold) of the SA2E dosage. By this dose reduction side effects were only moderate. This represents an enormous step forward in the targeted anti tumour therapy with recombinant fusion toxins. However, in all these studies a mixture of saponins was used. For the further successful development of a combinatorial anti cancer therapy with targeted toxins and saponins pure saponins are mandatory. This study was intended to isolate pure saponins from Gypsophila paniculata L. in order to scruntinize the toxicity enhancing properties of isolated Gypsophila saponins on targeted toxins. One of the four isolated saponins showed strong, one moderate and two no cytotoxicity enhancing properties. On the basis of these results we determined the structural prerequisites for the saponin-mediated toxicity enhancement of targeted toxins.