Gomesin peptides prevent proliferation and lead to the cell death of devil facial tumour disease cells

The Tasmanian devil faces extinction due to devil facial tumour disease (DFTD), a highly transmittable clonal form of cancer without available treatment. In this study, we report the cell-autonomous antiproliferative and cytotoxic activities exhibited by the spider peptide gomesin (AgGom) and gomesin-like homologue (HiGom) in DFTD cells. Mechanistically, both peptides caused a significant reduction at G0/G1 phase, in correlation with an augmented expression of the cell cycle inhibitory proteins p53, p27, p21, necrosis, exacerbated generation of reactive oxygen species and diminished mitochondrial membrane potential, all hallmarks of cellular stress. The screening of a novel panel of AgGom-analogues revealed that, unlike changes in the hydrophobicity and electrostatic surface, the cytotoxic potential of the gomesin analogues in DFTD cells lies on specific arginine substitutions in the eight and nine positions and alanine replacement in three, five and 12 positions. In conclusion, the evidence supports gomesin as a potential antiproliferative compound against DFTD disease.

• Publication year

  2018

• Venue

  Cell Death Discovery

• Publication date

  2018-02-14

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1038/s41420-018-0030-0PMID 29531816PMCID 5841354
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• The Immunomodulatory Small Molecule Imiquimod Induces Apoptosis in Devil Facial Tumour Cell Lines

  2016cited by this paper
• PD-L1 Is Not Constitutively Expressed on Tasmanian Devil Facial Tumor Cells but Is Strongly Upregulated in Response to IFN-γ and Can Be Expressed in the Tumor Microenvironment

  2016cited by this paper
• Mitochondria and Cancer.

  2016cited by this paper
• Mitogen‐activated Tasmanian devil blood mononuclear cells kill devil facial tumour disease cells

  2016cited by this paper
• Comparative study of the mechanism of action of the antimicrobial peptide gomesin and its linear analogue: The role of the β-hairpin structure.

  2015cited by this paper
• Doxorubicin and carboplatin trials in Tasmanian devils (Sarcophilus harrisii) with Tasmanian devil facial tumor disease.

  2015cited by this paper
• Structure-activity relationship of the antimicrobial peptide gomesin: the role of peptide hydrophobicity in its interaction with model membranes.

  2014cited by this paper
• Spider venomics: implications for drug discovery.

  2014cited by this paper
• p53 regulates a non-apoptotic death induced by ROS

  2013cited by this paper
• Reversible epigenetic down-regulation of MHC molecules by devil facial tumour disease illustrates immune escape by a contagious cancer

  2013cited by this paper
• Vincristine Chemotherapy Trials and Pharmacokinetics in Tasmanian Devils with Tasmanian Devil Facial Tumor Disease

  2013cited by this paper
• How the devil facial tumor disease escapes host immune responses

  2013cited by this paper
• Tumor suppression by p53: fall of the triumvirate?

  2012cited by this paper
• Definition and testing of the GROMOS force-field versions 54A7 and 54B7

  2011cited by this paper
• Revealing the lytic mechanism of the antimicrobial peptide gomesin by observing giant unilamellar vesicles.

  2010cited by this paper
• Transmission dynamics of Tasmanian devil facial tumor disease may lead to disease-induced extinction.

  2009cited by this paper
• Cationic amphiphilic peptides with cancer-selective toxicity.

  2009cited by this paper
• Contact networks in a wild Tasmanian devil (Sarcophilus harrisii) population: using social network analysis to reveal seasonal variability in social behaviour and its implications for transmission of devil facial tumour disease.

  2009cited by this paper
• GROMACS 4:  Algorithms for Highly Efficient, Load-Balanced, and Scalable Molecular Simulation.

  2008cited by this paper
• Effective topical treatment of subcutaneous murine B16F10-Nex2 melanoma by the antimicrobial peptide gomesin.

  2008cited by this paper
• Studies on anticancer activities of antimicrobial peptides.

  2008cited by this paper
• The role of hemocytes in the immunity of the spider Acanthoscurria gomesiana.

  2008cited by this paper
• Gomesin, a peptide produced by the spider Acanthoscurria gomesiana, is a potent anticryptococcal agent that acts in synergism with fluconazole.

  2007cited by this paper
• Towards a Case Definition for Devil Facial Tumour Disease: What Is It?

  2007cited by this paper
• Allograft theory: Transmission of devil facial-tumour disease

  2006cited by this paper
• Gene expression-based chemical genomics identifies rapamycin as a modulator of MCL1 and glucocorticoid resistance.

  2006cited by this paper
• Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors.

  2005cited by this paper
• Mitochondrial membrane potential regulates matrix configuration and cytochrome c release during apoptosis

  2003cited by this paper
• The solution structure of gomesin, an antimicrobial cysteine-rich peptide from the spider.

  2002cited by this paper
• Electrostatics of nanosystems: Application to microtubules and the ribosome

  2001cited by this paper
• VMD: visual molecular dynamics.

  1996cited by this paper

• No Evidence for Distinct Transcriptomic Subgroups of Devil Facial Tumor Disease (DFTD)

  2025cites this paper
• The cytotoxicity of gomesin peptides is mediated by the glycosphingolipid pathway and lipid-cholesterol interactions

  2025cites this paper
• Natural Gomesin-like Peptides with More Selective Antifungal Activities

  2024cites this paper
• Why to Study Peptides from Venomous and Poisonous Animals?

  2023cites this paper
• Unlocking the Potential of the Antimicrobial Peptide Gomesin: From Discovery and Structure–Activity Relationships to Therapeutic Applications

  2023cites this paper
• The structural conformation of the tachykinin domain drives the anti‐tumoural activity of an octopus peptide in melanoma BRAFV600E

  2022cites this paper
• Antimicrobial Peptides with Anti-Candida Activity

  2022cites this paper
• Modern venomics—Current insights, novel methods, and future perspectives in biological and applied animal venom research

  2022cites this paper
• Biosynthesis of Zinc Oxide Nanoparticles Using Hertia intermedia and Evaluation of its Cytotoxic and Antimicrobial Activities

  2021cites this paper
• ERK and mTORC1 Inhibitors Enhance the Anti-Cancer Capacity of the Octpep-1 Venom-Derived Peptide in Melanoma BRAF(V600E) Mutations

  2021cites this paper
• LXR stimulates a metabolic switch and reveals cholesterol homeostasis as a statin target in Tasmanian devil facial tumor disease.

  2021cites this paper
• Endocytosis and the Participation of Glycosaminoglycans Are Important to the Mechanism of Cell Death Induced by β-Hairpin Antimicrobial Peptides.

  2021cites this paper
• Sweet as honey, bitter as bile: mitochondriotoxic peptides and other therapeutic proteins isolated from animal tissues, for dealing with mitochondrial apoptosis.

  2020cites this paper
• Derivatives of gecko cathelicidin-related antioxidant peptide facilitate skin wound healing.

  2020cites this paper
• Recapitulation of the accessible interface of biopsy-derived canine intestinal organoids to study epithelial-luminal interactions

  2020cites this paper
• Revisiting the Interaction of Melittin with Phospholipid Bilayers: The Effects of Concentration and Ionic Strength

  2020cites this paper
• The unusual conformation of cross‐strand disulfide bonds is critical to the stability of β‐hairpin peptides

  2020cites this paper
• Versatile spider venom peptides and their medical and agricultural applications

  2019cites this paper
• The antiproliferative and apoptotic profile of gomesin against DFTD

  2018cites this paper
• The Biological and Biophysical Properties of the Spider Peptide Gomesin

  2018cites this paper