Influence of chain length on the anticancer activity of the antimicrobial peptide CAMEL with fatty acid modification

Ling Ma; Sujie Huang; Huan Xie; Panpan Ma; Bo Jia; Yufan Yao; Yuxuan Gao; Wenyuan Li; Jingjing Song; Wei Zhang

doi:10.1016/j.ejmech.2022.114557

Influence of chain length on the anticancer activity of the antimicrobial peptide CAMEL with fatty acid modification

Eur J Med Chem. 2022 Sep 5:239:114557. doi: 10.1016/j.ejmech.2022.114557. Epub 2022 Jun 23.

Authors

Ling Ma¹, Sujie Huang², Huan Xie³, Panpan Ma², Bo Jia², Yufan Yao², Yuxuan Gao¹, Wenyuan Li², Jingjing Song⁴, Wei Zhang⁵

Affiliations

¹ The Institute of Pharmacology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, China.
² Institute of Physiology, Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, China.
³ Department of Medical, Gansu Provincial Hospital, Lanzhou, 730000, China.
⁴ The Institute of Pharmacology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, China. Electronic address: songjj@lzu.edu.cn.
⁵ Institute of Physiology, Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, China; State Key Laboratory of Veterinary Etiological Biology, College of Veterinary Medicine, Lanzhou University, Lanzhou, 730000, China. Electronic address: zhangwei@lzu.edu.cn.

PMID: 35759906
DOI: 10.1016/j.ejmech.2022.114557

Abstract

Antimicrobial peptides (AMPs) display promising potential in cancer therapy. Modification with fatty acids is a simple and effective approach to improve the activity of AMPs. In the present study, we investigated the effects of fatty acid chain lengths on the anticancer activity, self-assembly and mechanism of action of CAMEL (CM15, KWKLFKKIGAVLKVL-NH₂), an amphipathic AMP with 15 amino acids. Conjugation of fatty acids could obviously improve the in vitro anticancer activity of CAMEL. Among the tested peptides, C12-CAMEL showed the highest anticancer activity, while C16-CAMEL killed cancer cells with the slowest kinetics. This may be related to the self-assembly of C12-CAMEL and C16-CAMEL, which could form spherical nanoparticles and tightened nanofibers, respectively. In addition, necrosis and necroptosis rather than apoptosis were the major mechanisms underlying the anticancer activity of CAMEL, C12-CAMEL and C16-CAMEL, implying that modification with fatty acids did not obviously alter the mechanism of action of CAMEL. Notably, C12-CAMEL, with high and rapid cell-killing activity, exhibited significantly stronger in vivo anticancer activity than CAMEL and C16-CAMEL. Overall, the present work suggests that the choice of a suitable fatty acid for structural modification is necessary for improving the anticancer activity of AMPs.

Keywords: Anticancer; Antimicrobial peptide; Fatty acid modification; Membrane disruption; Necroptosis; Self-assembly.

MeSH terms

Animals
Antimicrobial Peptides
Apoptosis
Camelus*
Fatty Acids* / chemistry
Fatty Acids* / pharmacology

Substances

Antimicrobial Peptides
Fatty Acids