MDA-MB-231 Breast Cancer Cells Resistant to Pleurocidin-Family Lytic Peptides Are Chemosensitive and Exhibit Reduced Tumor-Forming Capacity

Author:

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

Abstract

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 and RNA sequencing 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.

Funder

Breast Cancer Society of Canada

Natural Sciences and Engineering Research Council of Canada

Michael Smith Foundation for Health Research

Canadian Institutes of Health Research

Publisher

MDPI AG

Subject

Molecular Biology,Biochemistry

Reference24 articles.

1. Immune modulation by multifaceted cationic host defense (antimicrobial) peptides

2. Studies on anticancer activities of antimicrobial peptides

3. Obstacles and solutions to the use of antimicrobial peptides in the treatment of cancer;Hilchie,2010

4. The application of cationic antimicrobial peptides in cancer treatment: Laboratory investigations and clinical potential;Hilchie,2010

5. Pleurocidin-family cationic antimicrobial peptides are cytolytic for breast carcinoma cells and prevent growth of tumor xenografts

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