A NOVEL DERMASEPTIN PEPTIDE EXHIBITS ANTICANCER ACTIVITY VIA INDUCTION OF APOPTOSIS AND AUTOPHAGY

Qilin Long, Lei Wang, Yuxin Wu, Tianbao Chen and Chris Shaw

Department of Pharmacy, Queen's University Belfast, Belfast, United Kingdom

Abstract

A large number of antimicrobial peptides (AMPs) from frog skin secretions have been reported to date, many of which have been found to be effective anticancer agents. Elucidation of the molecular mechanism(s) of these peptides is crucial for developing novel therapeutic strategies and preventing treatment resistance. Here, we report the discovery of a novel dermaseptin peptide, named QUB3164, in Phyllomedusa sauvagei skin, which shows anti-proliferative effects against U251MG human glioblastoma cells, at 10-5M. By use of annexin-V imaging and immunoblotting probe, we also demonstrated that QUB3164 could induce apoptosis at a threshold concentration of 10-6M. In addition, further transcriptional and translational evidence showed that the peptide decreased U251MG cell viability not only by apoptosis, but also by autophagy, which revealed that U251MG cancer cells adapted to exogenous stress via both cytotoxic and cytoprotective signalling pathways. Therefore, for the first time, we have demonstrated the actions of two modes of programmed cell death triggered by an amphibian-sourced bioactive peptide and confirmed the involvement of apoptosis and autophagy in the resultant anticancer activities.

Keywords: Peptide, apoptosis, autophagy, skin secretion, signalling pathway.