MDA-MB-231 breast cancer cells resistant to pleurocidin-family lytic peptides are chemosensitive and exhibit reduced tumor-forming capacity

Ashley L. Hilchie, Erin E. Gill, Melanie R. Power Coombs, Reza Falsafi, Robert E.W. Hancock, David W. Hoskin

Research output: Contribution to journalArticle


Direct-acting anticancer (DAA) peptides are cytolytic peptides that show promise as novel anticancer agents. DAA peptides bind to anionic molecules that are abundant on cancer cells relative to normal healthy cells, which results in preferential killing of cancer cells. Due to the mechanism by which DAA peptides kill cancer cells, it was thought that resistance would be difficult to achieve. Here, we describe the generation and characterization of two MDA-MB-231 breast cancer cell-line variants with reduced susceptibility to pleurocidin-family and mastoparan DAA peptides. Peptide resistance correlated with deficiencies in peptide binding to cell-surface structures, suggesting that resistance was due to altered composition of the cell membrane. Peptide-resistant MDA-MB-231 cells were phenotypically distinct yet remained susceptible to chemotherapy. Surprisingly, neither of the peptide-resistant breast cancer cell lines was able to establish tumors in immune-deficient mice. Histological analysis andRNAsequencing suggested that tumorigenicity was impacted by alternations in angiogenesis and extracellular matrix composition in the peptide-resistant MDA-MB-231 variants. Collectively, these data further support the therapeutic potential of DAA peptides as adjunctive treatments for cancer.

Original languageEnglish
Article number1220
Pages (from-to)1-16
Number of pages16
Issue number9
Publication statusPublished - Sep 2020


  • Anticancer peptide
  • Breast cancer
  • Cytolysis
  • Peptide-resistance
  • Pleurocidin

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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