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.