Novel peptide dermaseptin‐PS1 exhibits anticancer activity via induction of intrinsic apoptosis signalling

Abstract

Antimicrobial peptides (AMP) secreted by the granular glands of frog skin have been widely reported to exhibit strong bacteriostatic and bactericidal activities. Many of them have been documented with potent antiproliferative effects on multiple cancer cells, many studies also suggested that AMPs exert their functions via disrupting cell membranes. However, whether and how other cell death induction mechanism is involved in mammalian cancer cells has rarely been investigated. In this study, a novel AMP named Dermaseptin‐PS1 was isolated and identified from Phyllomedusa sauvagei, it showed strong antimicrobial activities against three types of microorganisms. In vitro antiproliferative studies on human glioblastoma U‐251 MG cells indicated that Dermaseptin‐PS1 disrupted cell membranes at the concentrations of 10−5 M and above, while the cell membrane integrity was not affected when concentrations were decreased to 10−6 M or lower. Further examinations revealed that, at the relatively low concentration (10−6 M), Dermaseptin‐PS1 induced apoptosis through mitochondrial‐related signal pathway in U‐251 MG cells. Thus, for the first time, we report a novel frog skin derived AMP with anticancer property by distinct mechanisms, which largely depends on its concentration. Together, our study provides new insights into the mechanism‐illustrated drug design and the optimisation of dose control for cancer treatment in clinic.

Bioinformatic Analysis of 1000 Amphibian Antimicrobial Peptides Uncovers Multiple Length-Dependent Correlations for Peptide Design and Prediction

“…There are also other anticancer mechanisms. Dermaseptin-PS1 inhibits human glioblastoma U-251 MG cells (from cells frozen in Uppsala in 1969) via inducing apoptosis at a low micromolar concentration and disrupts cancer cell membranes at 10-fold the concentration [ 112 ]. Moreover, brevinin-1GHd was shown to inhibit proliferation of human cancer lines [ 113 ].…”

Bioinspired Bola-Type Peptide Dendrimers Inhibit Proliferation and Invasiveness of Glioblastoma Cells in a Manner Dependent on Their Structure and Amphipathic Properties

“…Recently, the application of cationic host defense peptides was rationalized for glioblastoma treatment by the studies of Riedl et al, who selectively targeted negatively charged phosphatidylserine molecules located on the external leaflet of the membranes [ 11 ] of melanoma, glioblastoma and a rhabdomyosarcoma cells as well as prostate and renal cancer cells by analogs of human Lactoferricin [ 12 , 13 ]. Following these findings, efficacy of several structurally different AMP’s alone [ 14 , 15 , 16 ] or as hybrid materials [ 5 , 17 , 18 , 19 , 20 ] was tested against glioblastoma cells and showed their substantial activity along with structure-dependent versatility of mechanism of action [ 21 , 22 , 23 ].…”

Peptide Dendrimers with Non-Symmetric Bola Structure Exert Long Term Effect on Glioblastoma and Neuroblastoma Cell Lines

“…This cationic and amphiphilic compound belongs to a large family of natural antimicrobial peptides (AMPs). Consequently, efficacy of various AMPs, alone [ 37 , 38 , 39 ] or as hybrid materials [ 40 , 41 , 42 , 43 , 44 ], was tested against GBM cells and showed their substantial activity along with structure-dependent versatility of mechanism of action [ 45 , 46 , 47 ]. Moreover, PS-targeting was successfully applied for the design of a new delivery systems for brain tumors imaging and therapy [ 48 , 49 ].…”