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Lookup NU author(s): Dr Frida Ponthan
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Antimicrobial peptides have been shown to exert cytotoxic activity towards cancer cells through their ability to interact with negatively charged cell membranes. In this study the cytotoxic effect of the antimicrobial peptide, LfcinB was tested in a panel of human neuroblastoma cell lines. LfcinB displayed a selective cytotoxic activity against both MYCN-amplified and non-MYCN-amplified cell lines. Non-transformed fibroblasts were not substantially affected by LfcinB. Treatment of neuroblastoma cells with LfcinB induced rapid destabilization of the cytoplasmic membrane and formation of membrane blebs. Depolarization of the mitochondria membranes and irreversible changes in the mitochondria morphology was also evident. Immuno- and fluorescence-labeled LfcinB revealed that the peptide co-localized with mitochondria. Furthermore, treatment of neuroblastoma cells with LfcinB induced cleavage of caspase-6, -7 and -9 followed by cell death. However, neither addition of the pan-caspase inhibitor, zVAD-fmk, or specific caspase inhibitors could reverse the cytotoxic effect induced by LfcinB. Treatment of established SH-SY-5Y neuroblastoma xenografts with repeated injections of LfcinB resulted in significant tumor growth inhibition. These results revealed a selective destabilizing effect of LfcinB on two important targets in the neuroblastoma cells, the cytoplasmic- and the mitochondria membrane.
Author(s): Eliassen LT, Berge G, Leknessund A, Wikman M, Lindin I, Løkke C, Ponthan FM, Johnsen JI, Sveinbjørnsson B, Kogner P, Flægstad T, Rekdal O
Publication type: Article
Publication status: Published
Journal: International Journal of Cancer
Year: 2006
Volume: 119
Issue: 3
Pages: 493-500
ISSN (print): 0020-7136
ISSN (electronic): 1097-0215
URL: http://dx.doi.org/10.1002/ijc.21886
DOI: 10.1002/ijc.21886
Notes: Journal Article Research Support, Non-U.S. Gov't United States
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