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

Citation

Fernandez-Rojo, MA and Deplazes, E and Pineda, SS and Brust, A and Marth, T and Wilhelm, P and Martel, N and Ramm, GA and Mancera, RL and Alewood, PF and Woods, GM and Belov, K and Miles, JJ and King, GF and Ikonomopoulou, MP, Gomesin peptides prevent proliferation and lead to the cell death of devil facial tumour disease cells, Cell Death Discovery, 4 Article 19. ISSN 2058-7716 (2018) [Refereed Article]


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The Author(s) 2018. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) http://creativecommons.org/licenses/by/4.0/

DOI: doi:10.1038/s41420-018-0030-0

Abstract

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.

Item Details

Item Type:Refereed Article
Keywords:cancer, chemotherapy, Tasmanian devil, devil facial tumour disease, cytotoxicity
Research Division:Medical and Health Sciences
Research Group:Oncology and Carcinogenesis
Research Field:Chemotherapy
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Cancer and Related Disorders
Author:Woods, GM (Professor Gregory Woods)
ID Code:125438
Year Published:2018
Deposited By:Menzies Institute for Medical Research
Deposited On:2018-04-17
Last Modified:2018-05-10
Downloads:0

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