As part of the innate immune system, HDPs are expressed in nearly every kind of organism, from plants over amphibians to mammals. Initially classified as exclusively antimicrobial active substances, HDPs have demonstrated significant cytotoxic effects against a wide range of malignant cells including e.g. melanoma, breast- and lung cancer. The oncolytic effect of HDPs depends on their amphipathic, cationic structure. The positive charge of the peptides is proposed to initiate electrostatic interaction with the negatively charged membrane of tumor cells which could lead to permeation of the peptide into the membrane and a subsequent complete membrane disruption. Despite the potent oncolytic activity of these peptides in vitro, studies in vivo are very limited, mainly because of their inactivation in serum, partially because of their binding to serum DAPT Gamma-secretase inhibitor components and their enzymatic degradation. This has led to the development of synthetic D-amino acid analogues. D-amino acid peptides could show potent oncolytic activity and high selectivity in prostate carcinoma and preserved their activity also in xenograft models in vivo. The differences between naturally occurring lytic Lcompared to artificially synthesized D-amino acid peptides is their modified structure. While in solution both peptides show unordered structure characteristics, in and on membranes they have different behaviors. L-amino acids often assume a-helical structures. Damino acids instead can bind better to negatively charged membranes of tumors than to zwitterionic membranes of normal mammalian cells. Another important point is the pH dependence of HDPs. Frequently tumor tissue possesses an acidic extracellular milieu because of the disordered metabolic and nutritional environment. Much current research is focused on designing HDPs which are only active in acidic environment, as this may be promising feature in oncolytic treatment. The host defense-like lytic peptide -K3H3L9 used in this study is composed of the D- and L-amino acids lysine, XAV939 side effects histidine and leucin. Histidine is protonated below pH 7. The acidic environment created by solid tumors activates the HDP by making it cationic. Therefore selectivity against malignant tissue is achieved. In previous studies the -K3H3L9 peptide has already shown an oncolytic activity against prostate carcinoma in cell culture and also in an in vivo xenograft model. The aim of this study was to assess the oncolytic activity of the D-amino acid peptide -K3H3L9 in an athymic and immunocompetent model and to analyze the potential of this peptide as a therapeutic option against STS. The metabolic activity was measured via MTT assay according to the standard protocol. Short: Cells were seeded in 96-well microtiter plates in a concentration of 16104 cells per well. The following day, cells were incubated in FCS-free media with different concentrations of -K3H3L9 for 24 hours. Thereafter the cells were incubated in fresh media containing Thiazolyl Blue Tetrazolium Bromid solution for another 4 hours.