Antimicrobial peptide TP4 induces ROS-mediated necrosis by triggering mitochondrial dysfunction in wild-type and mutant p53 glioblastoma cells

Bor Chyuan Su, Chieh Yu Pan, Jyh Yih Chen

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Antimicrobial peptide tilapia piscidin 4 (TP4) from Oreochromis niloticus exhibits potent bactericidal and anti-tumorigenic effects. In a variety of cancers, the mutation status of p53 is a decisive factor for therapeutic sensitivity. Therefore, we investigated the impact of p53 status on TP4-induced cytotoxicity in glioblastoma cell lines and the molecular mechanisms that govern cytotoxic effects. Both U87MG (wild-type/WT p53) and U251 (mutant p53) glioblastoma cell lines were sensitive to TP4-induced cytotoxicity. The necrosis inhibitors Necrostatin-1 and GSK’872 attenuated TP4-induced cytotoxicity, and TP4 treatment induced the release of cyclophilin A, a biomarker of necrosis. Moreover, TP4 induced mitochondrial hyperpolarization and dysfunction, which preceded the elevation of intracellular reactive oxygen species, DNA damage, and necrotic cell death in both U87MG and U251 glioblastoma cells. p38 was also activated by TP4, but did not contribute to cytotoxicity. SB202190, a specific p38 inhibitor, enhanced TP4-induced oxidative stress, mitochondrial dysfunction, and cytotoxicity, suggesting a protective role of p38. Furthermore, TP4-induced cytotoxicity, oxidative stress, phosphorylation of p38, and DNA damage were all attenuated by the mitochondrial-targeted reactive oxygen species (ROS) scavenger MitoTEMPO, or the reactive oxygen species scavenger N-acetyl-L-cysteine. Based on these data, we conclude that TP4 induces necrosis in both WT and mutant p53 glioblastoma cells through a mitochondrial ROS-dependent pathway.

Original languageEnglish
Article number171
JournalCancers
Volume11
Issue number2
DOIs
Publication statusPublished - Feb 1 2019
Externally publishedYes

Keywords

  • Antimicrobial peptide
  • DNA damage
  • Glioblastoma
  • Necrosis
  • p53
  • ROS
  • Tilapia piscidin 4

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Antimicrobial peptide TP4 induces ROS-mediated necrosis by triggering mitochondrial dysfunction in wild-type and mutant p53 glioblastoma cells'. Together they form a unique fingerprint.

  • Cite this