title: Oncolytic designer host defense peptide suppresses growth of human liposarcoma.
abstract: Sarcomas display a rare and heterogeneous group of tumors. Treatment options are limited. Host defense peptides (HDPs), effector molecules of the innate immune system, might provide a more effective treatment option. The aim of our study was to analyze the oncolytic activity and mode of action of a designer HDP. In vitro, the human liposarcoma cell line SW-872 and primary human fibroblasts as a control were exposed to [D]-K(3)H(3)L(9), a 15-mer D,L-amino acid designer peptide. Cell growth (MTT assay), proliferation (BrdU assay) and genotoxicity (TUNEL assay) were analyzed. The mode of action was examined via fluorescence-activated cell sorter (FACS) analysis and confocal laser scanning microscopy. In vivo, [D]-K(3)H(3)L(9) (n = 7) was administered intratumorally in a SW-872 xenograft mouse model (Foxn1nu/nu). Phosphate buffered saline served as a control (n = 5). After 4 weeks, tumor sections were histologically analyzed with respect to proliferation, cytotoxicity, vessel density and signs of apoptosis and necrosis, respectively. In vitro, [D]-K(3)H(3)L(9) highly significantly (p < 0.01) inhibited cell metabolism and proliferation. TUNEL assay revealed corresponding genotoxicity. FACS analysis suggested induction of necrosis as a cause of cell death. The mean tumor volume of the control group exponentially increased sevenfold, whereas the mean tumor growth was negligible in the treatment group. Macroscopically, [D]-K(3)H(3)L(9) induced full tumor remission in 43% of treated animals and partial remission in 43%. Vessel density was significantly reduced by 52%. Morphological analyses supported the hypothesis of cancer cell killing by necrosis. In summary, [D]-K(3)H(3)L(9) exerts very promising oncolytic activity on liposarcoma cells. Our study demonstrates the potential of HDPs as a novel therapeutic option in future soft tissue sarcoma therapy.
authors: Department of Plastic and Reconstructive Surgery, BG University Hospital Bergmannsheil, Ruhr University Bochum, Bochum, Nordrhein-Westfalen, Germany. lars.steinstraesser@ruhr-uni-bochum.de
authors: Lars
authors: L
authors: Steinstraesser
authors: Cornelius
authors: C
authors: Schubert
authors: Jennifer
authors: J
authors: Hauk
authors: Mustafa
authors: M
authors: Becerikli
authors: Ingo
authors: I
authors: Stricker
authors: Manfred
authors: M
authors: Koeller
authors: Hanns
authors: H
authors: Hatt
authors: Monika
authors: M
authors: von Duering
authors: Yechiel
authors: Y
authors: Shai
authors: Hans-Ulrich
authors: HU
authors: Steinau
authors: Frank
authors: F
authors: Jacobsen
mesh_terms: D000818:Animals; D002455:Cell Division; D005434:Flow Cytometry; D006801:Humans; D020287:In Situ Nick-End Labeling; D008080:Liposarcoma / Q000473:pathology*; D051379:Mice; D018613:Microscopy, Confocal; D050130:Oncolytic Virotherapy; D010455:Peptides / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D010455:Peptides