Saponins as Tool for Improved Targeted Tumor Therapies

H.      Fuchs; D.      Bachran; H.      Panjideh; N.      Schellmann; A.      Weng; M.   F.   Melzig; M.      Sutherland; C.      Bachran

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 μM. A drawback of saponins in tumor therapy is the nontargeted 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.

Keywords: Cancer, chimeric toxins, cleavable adapters, epidermal growth factor receptor, glycosylated triterpenoids, ribosome- inactivating proteins, saponins, targeted tumor therapy