Antimicrobial peptide FF/CAP18 induces apoptotic cell death in HCT116 colon cancer cells via changes in the metabolic profile

Kengo Kuroda, Tomokazu Fukuda, Hiroshi Isogai, Kazuhiko Okumura, Marija Krstic-Demonacos, Emiko Isogai

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1516-1526
Number of pages11
JournalInternational journal of oncology
Volume46
Issue number4
DOIs
Publication statusPublished - 2015 Apr 1

Keywords

  • Antimicrobial peptide
  • Apoptosis
  • CE-TOFMS
  • HCT116 cell line
  • Metabolome analysis

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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