Pro-necrotic Activity of Cationic Mastoparan Peptides in Human Glioblastoma Multiforme Cells Via Membranolytic Action

Mol Neurobiol. 2018 Jul;55(7):5490-5504. doi: 10.1007/s12035-017-0782-1. Epub 2017 Sep 30.

Abstract

Glioblastoma multiforme is the most common and lethal malignant brain tumor. Because of its complexity and heterogeneity, this tumor has become resistant to conventional therapies and the available treatment produces multiple side effects. Here, using multiple experimental approaches, we demonstrate that three mastoparan peptides-Polybia-MP1, Mastoparan X, and HR1-from solitary wasp venom exhibit potent anticancer activity toward human glioblastoma multiforme cells. Importantly, the antiglioblastoma action of mastoparan peptides occurs by membranolytic activity, leading to necrosis. Our data also suggest a direct relation between mastoparan membranolytic potency and the presence of negatively charged phospholipids like phosphatidylserine. Collectively, these data may warrant additional studies for mastoparan peptides as new agents for the treatment of glioblastoma multiforme brain tumor.

Keywords: Cationic peptide; Glioblastoma; Mastoparan; Necrosis; Phosphatidylserine.

MeSH terms

  • Amino Acid Sequence
  • Calcium / metabolism
  • Cations
  • Cell Line, Tumor
  • Cell Membrane / pathology*
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism
  • Cell Shape / drug effects
  • Cell Survival / drug effects
  • Glioblastoma / drug therapy*
  • Glioblastoma / pathology
  • Glioblastoma / ultrastructure
  • Humans
  • Intercellular Signaling Peptides and Proteins
  • Membrane Potential, Mitochondrial / drug effects
  • Necrosis
  • Peptides / chemistry
  • Peptides / pharmacology
  • Peptides / therapeutic use*
  • Protein Structure, Secondary
  • Wasp Venoms / chemistry
  • Wasp Venoms / pharmacology
  • Wasp Venoms / therapeutic use*

Substances

  • Cations
  • Intercellular Signaling Peptides and Proteins
  • Peptides
  • Wasp Venoms
  • mastoparan
  • Calcium