Anti-Infective Properties of Anti-Cancer Cationic Peptides containing Survivin or Apolipoprotein E Sequences

Abstract

Specific intracellular pathways regulated by Apolipoprotein E (ApoE), a PP2A activator or survivin, an inhibitor of Heat Shock Proteins (HSP), can impact human diseases including cancers. In this study, we have initially observed that anti-tumor Tat-survivin (shepherdin-Tat), and ApoE mimetics, Cog or Tat-Cog &Cog-Tat, peptides contained cationic sequences that share similar physical characteristics with LL17-32, a short active sequence of the anti-microbial human cathelecidin peptide. Furthermore, to investigate the potential host defense properties of these peptidic sequences we have comparatively analyzed anti-tumor and anti-bacterial properties of shepherdin-Tat and ApoE mimetic peptides with the human LL17-32 cathelecidin sequence using U87G cells, a relevant human  glioblastoma model, and a Group B Streptococcus agalactiae NEM316 ΔdltA that is highly sensitive to human LL17-32 cathelecidin. This study highligts two major insights indicating that similarly, to LL37 or LL17-32 cathelecidin sequences, shepherdin-Tat and ApoE mimetic peptides firstly impairs the growth of S. agalactiae NEM 316 dltA strain, and secondly inhibited the survival of human glioblastoma U87G cells. In conclusion, together, our results clearly indicate that cationic peptides with survivin and ApoE anti-tumor sequences, including scrambled shepherdinTat, a previously described biologically inactive anti-cancer molecule, behave as cathelecidin-like anti-infective host defense molecules. In addition, we identified hybrid Cog-Tat/Tat-Cog peptides as potential and highly potent therapeutic molecules with anti-glioblastoma and anti-bacterial effects.