Document Detail


Suppression of soft tissue sarcoma growth by a host defense-like lytic peptide.
MedLine Citation:
PMID:  21483840     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Soft tissue sarcoma (STS) is an anatomically and histologically heterogeneous neoplasia that shares a putative mesenchymal cell origin. The treatment with common chemotherapeutics is still unsatisfying because of association with poor response rates. Although evidence is accumulating for potent oncolytic activity of host defense peptides (HDPs), their potential therapeutic use is often limited by poor bioavailability and inactivation in serum. Therefore, we tested the designer host defense-like lytic D,L-amino acid peptide [D]-K3H3L9 on two STS cell lines in vitro and also in an athymic and syngeneic mouse model. In recent studies the peptide could show selectivity against prostate carcinoma cells and also an active state in serum.
METHODS: In vitro the human synovial sarcoma cell line SW982, the murine fibrosarcoma cell line BFS-1 and primary human fibroblasts as a control were exposed to [D]-K3H3L9, a 15mer D,L-amino acid designer HDP. Cell vitality in physiological and acidic conditions (MTT-assay), cell growth (BrdU) and DNA-fragmentation (TUNEL) were investigated. Membrane damage at different time points could be analyzed with LDH assay. An antibody against the tested peptide and recordings using scanning electron microscopy could give an inside in the mode of action. In vivo [D]-K3H3L9 was administered intratumorally in an athymic and syngeneic (immunocompetent) mouse model with SW982 and BFS-1 cells, respectively. After three weeks tumor sections were histologically analyzed.
RESULTS: The peptide exerts rapid and high significant cytotoxicity and antiproliferating activity against the malignant cell lines, apparently via a membrane disrupting mode of action. The local intratumoral administration of [D]-K3H3L9 in the athymic and syngeneic mice models significantly inhibited tumor progression. The histological analyses of the tumor sections revealed a significant antiproliferative, antiangiogenic activity of the treatment group.
CONCLUSION: These findings demonstrate the in vitro and in vivo oncolytic activity of [D]-K3H3L9 in athymic and syngeneic mouse models.
Authors:
Lars Steinstraesser; Jennifer Hauk; Cornelius Schubert; Sammy Al-Benna; Ingo Stricker; Hanns Hatt; Yechiel Shai; Hans-Ulrich Steinau; Frank Jacobsen
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-03-31
Journal Detail:
Title:  PloS one     Volume:  6     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2011  
Date Detail:
Created Date:  2011-04-12     Completed Date:  2011-08-25     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e18321     Citation Subset:  IM    
Affiliation:
Laboratory for Wound Healing and Molecular Oncology, Department of Plastic Surgery, BG University Hospital Bergmannsheil, Ruhr University Bochum, Bochum, North Rhine-Westphalia, Germany. Lars.Steinstraesser@rub.de
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MeSH Terms
Descriptor/Qualifier:
Animals
Antineoplastic Agents / adverse effects,  pharmacology*,  therapeutic use*
Cell Line, Tumor
Cell Survival / drug effects
Cells, Cultured
DNA Fragmentation / drug effects
Enzyme-Linked Immunosorbent Assay
Hemolysis / drug effects
Humans
Hydrogen-Ion Concentration
Mice
Mice, Inbred BALB C
Peptides / adverse effects,  pharmacology*,  therapeutic use*
Sarcoma / drug therapy*
Soft Tissue Neoplasms / drug therapy*
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Peptides
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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