In this study we detected typical signs of membrane disruption. The premature LDH release gives a hint of disruption of the membrane integrity as a basic cause of the decreased cell vitality. By labeling the peptide via a specific primary antibody we could show a destroyed cell membrane after 4 hours of incubation with a lethal dose of -K3H3L9. These results were further verified by using scanning electron microscopy. The cationic peptide may bind to the anionic structures of the malignant cell membrane in a carpetlike manner. After reaching a threshold concentration the peptide may penetrate the membrane leading to a depolarization and death of the cell. Another reason for this selective membrane disruption is the relatively high number of microvilli projections on tumor cells. This leads to a larger surface and to the possibility of higher levels of HDP interaction. Due to the strong membranolytic activity of -K3H3L9 tumor cells are probably not capable to develop resistance. In previous studies bacteria treated with cationic HDPs did not show any resistance against the administered peptides. In vivo, two xenograft SP600125 JNK inhibitor models were used. Human synovial sarcoma cells were injected into athymic, immune deficient nude mice. Relatively few studies on oncolytic activity of HDPs have been performed in syngeneic models. Immunocompetent mouse models possess the advantage of investigating possible immunomodulatory properties of the peptides. Here the immunocompetent C57BL/6 mice model was treated with syngeneic murine fibrosarcoma cells. BFS-1 cells, originally induced in a female C57BL/6 mouse after treatment with methylcholanthrene, are now able to produce a tumor in an immunocompetent mouse model. Due to its intact immune system this model is closer related to clinical FG-4592 HIF inhibitor situations. Furthermore the model allows investigating the potential involvement of HDPs in the innate and adaptive immune system. Here -K3H3L9 could show significant oncolytic activity in both sarcoma xenograft models. Tumors treated with the carrier control PBS show an exponential growth, whereas tumors treated with the -K3H3L9 show partial or in two cases also total remission of the tumor. An antiproliferating activity could be demonstrated in histological and immunohistological samples after treatment with the peptide. In addition to the potent inhibition of tumor growth the immunohistochemical laminin-staining of the tumors treated with -K3H3L9 revealed a significant decrease in vasculature compared with untreated mice ). This may be the result of either a reduced cancer cells density, yet unknown, direct vascular targeting of the peptide or even a possible induction of angiogenic inhibiting factors. Soft tissue sarcoma are often markedly angiogenic and highly dependent on their vasculature for primary tumor growth as well as the development of metastases.