Pardaxin, a Fish Antimicrobial Peptide, Exhibits Antitumor Activity toward Murine Fibrosarcoma in Vitro and in VivoReportar como inadecuado




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1

Department of Aquaculture, National Taiwan Ocean University, Keelung 202, Taiwan

2

Marine Research Station, Institute of Cellular and Organismic Biology, Academia Sinica, 23-10 Dahuen Rd., Jiaushi, Ilan 262, Taiwan

3

Institute of Cellular and Organismic Biology, Academia Sinica, Taipei 115, Taiwan



These authors contributed equally to this work.





*

Authors to whom correspondence should be addressed.



Abstract The antitumor activity of pardaxin, a fish antimicrobial peptide, has not been previously examined in in vitro and in vivo systems for treating murine fibrosarcoma. In this study, the antitumor activity of synthetic pardaxin was tested using murine MN-11 tumor cells as the study model. We show that pardaxin inhibits the proliferation of MN-11 cells and reduces colony formation in a soft agar assay. Transmission electron microscopy TEM showed that pardaxin altered the membrane structure similar to what a lytic peptide does, and also produced apoptotic features, such as hollow mitochondria, nuclear condensation, and disrupted cell membranes. A qRT-PCR and ELISA showed that pardaxin induced apoptosis, activated caspase-7 and interleukin IL-7r, and downregulated caspase-9, ATF 3, SOCS3, STAT3, cathelicidin, p65, and interferon IFN-γ suggesting that pardaxin induces apoptosis through the death receptor-nuclear factor NF-κB signaling pathway after 14 days of treatment in tumor-bearing mice. An antitumor effect was observed when pardaxin 25 mg-kg; 0.5 mg-day was used to treat mice for 14 days, which caused significant inhibition of MN-11 cell growth in mice. Overall, these results indicate that pardaxin has the potential to be a novel therapeutic agent to treat fibrosarcomas. View Full-Text

Keywords: pardaxin; fibrosarcoma; antitumor pardaxin; fibrosarcoma; antitumor





Autor: Shu-Ping Wu 1,†, Tsui-Chin Huang 2,†, Ching-Chun Lin 3, Cho-Fat Hui 3,* , Cheng-Hui Lin 1 and Jyh-Yih Chen 2,*

Fuente: http://mdpi.com/



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