Distribution of positively charged amino acid residues in antimicrobial peptide epinecidin-1 is crucial for in vitro glioblastoma cytotoxicity and its underlying mechanisms

Bor Chyuan Su, Tsung Han Wu, Chun Hua Hsu, Jyh Yih Chen

研究成果: 雜誌貢獻文章同行評審

4 引文 斯高帕斯(Scopus)

摘要

Epinecidin-1 (epi) was identified from orange-spotted grouper (Epinephelus coioides) and exhibits diverse biological activities. The aims of this study were to investigate how the distribution of positively charged amino acid residues affects epi-mediated cytotoxicity and to examine the molecular mechanism underlying epi-induced cytotoxicity in U87MG human glioblastoma cells. MTS/PMS and trypan blue exclusion assay were used to measure cell viability. Necrotic cell death was confirmed by detecting cyclophilin A release and propidium iodide incorporation. DNA damage was evaluated by measuring phosphorylated H2AX. Intracellular reactive oxygen species (ROS) were analyzed by flow cytometry using dihydroergotamine. Mitochondrial membrane potential was detected by flow cytometry using tetramethylrhodamine, ethyl ester. Overall, we found that epi caused cytotoxicity in U87MG cells by inducing DNA damage and necrosis through mitochondrial hyperpolarization and subsequent ROS production. The proper folding of epi into an α-helical structure was essential for epi-mediated anti-glioblastoma effects. In addition, NFκB signaling was activated in U87MG cells after exposure to epi. Suppression of NFκB further enhanced epi-induced cytotoxicity, ROS generation and DNA damage, indicating that NFκB may play a protective role in epi-induced cytotoxicity. Our findings may be useful for the design and improvement of antimicrobial peptides with anti-cancer activity.
原文英語
文章編號108904
期刊Chemico-Biological Interactions
315
DOIs
出版狀態已發佈 - 一月 5 2020

ASJC Scopus subject areas

  • 毒理學

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