title: Antimicrobial peptide FF/CAP18 induces apoptotic cell death in HCT116 colon cancer cells via changes in the metabolic profile.
abstract: Metabolic reprogramming is one of the hallmarks of cancer and can be targeted by therapeutic agents. We previously reported that cathelicidin-related or modified antimicrobial peptides, such as FF/CAP18, have antiproliferative effects on the squamous cell carcinoma cell line SAS-H1, and the colon carcinoma cell line HCT116. Although antimicrobial peptides have potential use in the development of new therapeutic strategies, their effects on the metabolism of cancer cells are poorly understood. Here, we investigated changes in the levels of metabolites in HCT116 cells caused by FF/CAP18, via capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS). Analysis of the 177 intracellular metabolites and 113 metabolites in conditioned medium that were detected by CE-TOFMS, revealed dramatic changes in the metabolic profile of HCT116 cells after treatment with FF/CAP18. The metabolic profile showed that the levels of most metabolites in the major metabolic pathways supported the rapid proliferation of cancer cells. Purine metabolism, glycolysis, and the TCA cycle, were altered in FF/CAP18-treated cells in a dose-dependent manner. Our present study provides mechanistic insights into the anticancer effects of antimicrobial peptides that show great potential as new therapies for colon cancer.
authors: Graduate School of Agricultural Science, Tohoku University, Aoba-ku, Sendai 981-8555, Japan.
authors: Kengo
authors: K
authors: Kuroda
authors: Graduate School of Agricultural Science, Tohoku University, Aoba-ku, Sendai 981-8555, Japan.
authors: Tomokazu
authors: T
authors: Fukuda
authors: Animal Research Center, Sapporo Medical University, Sapporo 060-8556, Japan.
authors: Hiroshi
authors: H
authors: Isogai
authors: Department of Oral and Maxillofacial Surgery, School of Dentistry, Health Sciences University of Hokkaido, Hokkaido 061-0293, Japan.
authors: Kazuhiko
authors: K
authors: Okumura
authors: School of Environment and Life Sciences, College of Science and Technology, Cockcroft Building, University of Salford, Salford M5 4WT, UK.
authors: Marija
authors: M
authors: Krstic-Demonacos
authors: Graduate School of Agricultural Science, Tohoku University, Aoba-ku, Sendai 981-8555, Japan.
authors: Emiko
authors: E
authors: Isogai
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D045325:HCT116 Cells; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods; D055442:Metabolome; D055432:Metabolomics / Q000379:methods; D054804:Cathelicidins
chemical_list: D023181:Antimicrobial Cationic Peptides; D000970:Antineoplastic Agents; D054804:Cathelicidins