Strategy to Enhance Anticancer Activity and Induced Immunogenic Cell Death of Antimicrobial Peptides by Using Non-Nature Amino Acid Substitutions.
Journal
Biomedicines
Journal Volume
10
Journal Issue
5
ISSN
2227-9059
Date Issued
2022-05-09
Author(s)
Abstract
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.
Subjects
DAMPs
antimicrobial peptides
bulky non-nature amino acid
cancer
membrane integrity
oncolytic peptides
SDGs
Type
journal article