The investigation of structural requirements for saponins to enable synergistic cytotoxicity with type-I-RIP/lectins

Saponins and lectins, especially the naturally very low cytotoxic activity showing type-I-RIP (ribosome-inactivating proteins type I)/lectins exhibit a synergistic cytotoxicity when applied to cancer cells [1]. The pre-appliance of certain saponins can drastically amplify the cytotoxicity of the type-I-RIP [2, 3] and has become a promising strategy in anti-cancer research [2]. These saponins may also minimize the required effective dose of these very expensive (especially when linked to human antibodies and natural ligands) and time-consuming to purify/to create substances [5].

In our work we search for new saponins from plant-extracts capable of increasing the cytotoxicity of the naturally very low cytotoxic activity showing lectin saporin, considered as a standard type-I-RIP. The spotlight of our research is put on the plant-family of Caryophyllaceae, but saponins from other plant-families were also tested when fulfilling certain structural requirements. The investigation of these structural requirements that saponins have to fulfill to execute the synergistic cytotoxicity is in the focus of our work. All tests were performed in a cell culture model using ECV-304 cells. The cytotoxicity was measured by MTT assay and DNA quantification.

References: [1] Hebestreit, P., Melzig, M.F. (2003) Planta Med. 69:921–925. [2] Hebestreit, P. et al. (2006) Toxicon 47:330–335. [3] Weng, A. et al. (2008) Chem. Biol. Int. 176:204–211. [4] Bachran, C. et al. (2009)J. Immunother. 32:713–725. [5] Bachran, C. et al. (2010) Brit. J. Pharmacol. 159:345–352.