Antitumor Activity and Mechanism of Action of the Antimicrobial Peptide AMP-17 on Human Leukemia K562 Cells.

Content Provider	Europe PMC
Author	Tian, Zhuqing Yang, Longbing Huang, Mingjiao Sun, Chaoqin Chen, Mingming Zhao, Wenjing Peng, Jian Guo, Guo
Editor	Rogozhin, Eugene A.
Copyright Year	2022
Abstract	Cancer is one of the most common malignant diseases in the world. Hence, there is an urgent need to search for novel drugs with antitumor activity against cancer cells. AMP-17, a natural antimicrobial peptide derived from Musca domestica, has antimicrobial activity against Gram-positive bacteria, Gram-negative bacteria, and fungi. However, its antitumor activity and potential mechanism of action in cancer cells remain unclear. In this study, we focused on evaluating the in vitro antitumor activity and mechanism of AMP-17 on leukemic K562 cells. The results showed that AMP-17 exhibited anti-proliferative activity on K562 cells with an IC50 value of 58.91 ± 3.57 μg/mL. The membrane integrity of K562 was disrupted and membrane permeability was increased after AMP-17 action. Further observation using SEM and TEM images showed that the cell structure of AMP-17-treated cells was disrupted, with depressions and pore-like breaks on the cell surface, and vacuolated vesicles in the cytoplasm. Furthermore, further mechanistic studies indicated that AMP-17 induced excessive production of reactive oxygen species and calcium ions release in K562 cells, which led to disturbance of mitochondrial membrane potential and blocked ATP synthesis, followed by activation of Caspase-3 to induce apoptosis. In conclusion, these results suggest that the antitumor activity of AMP-17 may be achieved by disrupting cell structure and inducing apoptosis. Therefore, AMP-17 is expected to be a novel potential agent candidate for leukemia treatment.
Journal	Molecules
Volume Number	27
DOI	10.3390/molecules27228109
PubMed Central reference number	PMC9697079
Issue Number	22
PubMed reference number	36432210
e-ISSN	14203049
Language	English
Publisher	Molecular Diversity Preservation International (MDPI)
Publisher Date	2022-11-21
Access Restriction	Open
Subject Keyword	antimicrobial peptides AMP-17 human leukemia K562 cells anti-tumor membrane-disruption apoptosis
Content Type	Text
Resource Type	Article
Subject	Physical and Theoretical Chemistry Medicine Chemistry Drug Discovery Pharmaceutical Science Analytical Chemistry Molecular Medicine Organic Chemistry