https://scholars.lib.ntu.edu.tw/handle/123456789/561293
標題: | Distribution of positively charged amino acid residues in antimicrobial peptide epinecidin-1 is crucial for in vitro glioblastoma cytotoxicity and its underlying mechanisms | 作者: | Su, B.-C. Wu, T.-H. CHUN-HUA HSU Chen, J.-Y. |
關鍵字: | Antimicrobial peptide; Epinecidin-1; Glioblastoma; Mitochondria; NFκB; ROS | 公開日期: | 2020 | 卷: | 315 | 來源出版物: | Chemico-Biological Interactions | 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. ? 2019 Elsevier B.V. |
URI: | https://www.scopus.com/inward/record.url?eid=2-s2.0-85075215401&partnerID=40&md5=5aa5e075d4ae7213d8c5b7998cb180a0 https://scholars.lib.ntu.edu.tw/handle/123456789/561293 |
DOI: | 10.1016/j.cbi.2019.108904 | SDG/關鍵字: | amino acid; antineoplastic agent; cyclophilin A; dihydroergotamine; epinecidin 1; ester derivative; ethyl ester; histone H2AX; immunoglobulin enhancer binding protein; polypeptide antibiotic agent; propidium iodide; reactive oxygen metabolite; tetramethylrhodamine; trypan blue; unclassified drug; antimicrobial cationic peptide; fish protein; immunoglobulin enhancer binding protein; reactive oxygen metabolite; alpha helix; antineoplastic activity; Article; cell death; cell viability; concentration (parameter); controlled study; cytotoxicity; DNA damage; electricity; enzyme release; Epinephelus coioides; flow cytometry; glioblastoma; glioblastoma cell line; human; human cell; hyperpolarization; in vitro study; mitochondrial membrane potential; MTS assay; protein folding; protein phosphorylation; signal transduction; trypan blue assay; apoptosis; cell survival; drug effect; glioblastoma; metabolism; mitochondrial membrane potential; mitochondrion; tumor cell line; Amino Acids; Antimicrobial Cationic Peptides; Apoptosis; Cell Line, Tumor; Cell Survival; DNA Damage; Fish Proteins; Glioblastoma; Humans; Membrane Potential, Mitochondrial; Mitochondria; NF-kappa B; Reactive Oxygen Species; Signal Transduction |
顯示於: | 農業化學系 |
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