Cheah Yu-Huan, Liu Chun-Yu, Yip Bak-Sau, Wu Chih-Lung, Peng Kuang-Li, Cheng Jya-Wei
Department of Medical Science, Institute of Biotechnology, National Tsing Hua University, Hsinchu 300, Taiwan.
Department of Neurology, National Taiwan University Hospital Hsinchu Branch, Hsinchu 300, Taiwan.
Biomedicines. 2022 May 9;10(5):1097. doi: 10.3390/biomedicines10051097.
There is an urgent and imminent need to develop new agents to fight against cancer. In addition to the antimicrobial and anti-inflammatory activities, many antimicrobial peptides can bind to and lyse cancer cells. P-113, a 12-amino acid clinically active histatin-rich peptide, was found to possess anti- activities but showed poor anticancer activity. Herein, anticancer activities and induced immunogenic cancer cell death of phenylalanine-(Phe-P-113), β-naphthylalanine-(Nal-P-113), β-diphenylalanine-(Dip-P-113), and β-(4,4'-biphenyl)alanine-(Bip-P-113) substituted P-113 were studied. Among these peptides, Nal-P-113 demonstrated the best anticancer activity and caused cancer cells to release potent danger-associated molecular patterns (DAMPs), such as reactive oxygen species (ROS), cytochrome c, ATP, and high-mobility group box 1 (HMGB1). These results could help in developing antimicrobial peptides with better anticancer activity and induced immunogenic cell death in therapeutic applications.
迫切需要开发新的抗癌药物。除了具有抗菌和抗炎活性外，许多抗菌肽还能与癌细胞结合并使其裂解。P-113是一种含12个氨基酸且富含组蛋白的具有临床活性的肽，已发现它具有抗……活性，但抗癌活性较差。在此，研究了苯丙氨酸取代的P-113（Phe-P-113）、β-萘丙氨酸取代的P-113（Nal-P-113）、β-二苯丙氨酸取代的P-113（Dip-P-113）和β-（4,4'-联苯）丙氨酸取代的P-113（Bip-P-113）的抗癌活性及诱导的免疫原性癌细胞死亡。在这些肽中，Nal-P-113表现出最佳的抗癌活性，并使癌细胞释放出强效的危险相关分子模式（DAMPs），如活性氧（ROS）、细胞色素c、三磷酸腺苷（ATP）和高迁移率族蛋白B1（HMGB1）。这些结果有助于在治疗应用中开发具有更好抗癌活性和诱导免疫原性细胞死亡的抗菌肽。
