Strategy to Enhance Anticancer Activity and Induced Immunogenic Cell Death of Antimicrobial Peptides by Using...

Area of Science:

• Biochemistry
• Molecular Biology
• Immunology

Background:

• Antimicrobial peptides (AMPs) exhibit potential anticancer properties by binding and lysing cancer cells.
• The histatin-rich peptide P-113, while effective against Candida, displays limited anticancer efficacy.
• Developing novel peptide-based cancer therapeutics is crucial due to the urgent need for new cancer-fighting agents.

Purpose of the Study:

• To investigate the anticancer activities of P-113 substituted with various amino acids: phenylalanine (Phe-P-113), β-naphthylalanine (Nal-P-113), β-diphenylalanine (Dip-P-113), and β-(4,4'-biphenyl)alanine (Bip-P-113).
• To evaluate the capacity of these modified peptides to induce immunogenic cancer cell death.
• To identify specific danger-associated molecular patterns (DAMPs) released by cancer cells upon treatment.

Main Methods:

• Chemical synthesis of modified P-113 peptides.
• In vitro assessment of anticancer activity against cancer cell lines.
• Analysis of cancer cell death induction and DAMPs release, including reactive oxygen species (ROS), cytochrome c, ATP, and high-mobility group box 1 (HMGB1).

Main Results:

• Nal-P-113 exhibited the most potent anticancer activity among the tested peptide derivatives.
• Nal-P-113 treatment induced significant cancer cell death.
• Cancer cells treated with Nal-P-113 released substantial amounts of DAMPs, including ROS, cytochrome c, ATP, and HMGB1.

Conclusions:

• Substitution with specific amino acids can enhance the anticancer efficacy of P-113.
• Nal-P-113 is a promising candidate for developing novel cancer therapeutics due to its potent anticancer activity and ability to induce immunogenic cell death.
• The induction of DAMPs release by Nal-P-113 suggests a mechanism for stimulating anti-tumor immune responses.