Gomesin peptides prevent proliferation and lead to the cell death of devil facial tumour disease cells
Fernandez-Rojo, Manuel A., Deplazes, Evelyne, Pineda, Sandy S., Brust, Andreas, Marth, Tano, Wilhelm, Patrick, Martel, Nick, Ramm, Grant A., Mancera, Ricardo L., Alewood, Paul F., Woods, Gregory M., Belov, Katherine, Miles, John J., King, Glenn F., Ikonomopoulou, Maria P., and UNSPECIFIED (2018) Gomesin peptides prevent proliferation and lead to the cell death of devil facial tumour disease cells. Cell Death Discovery, 4. 19. pp. 1-11.
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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 ID: | 56645 |
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| Item Type: | Article (Research - C1) |
| ISSN: | 2058-7716 |
| Copyright Information: | © The Author(s) 2018. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licensesby/4.0/. |
| Funders: | Madrid Government of Spain (MGS), Marie Curie (MC), Swiss National Science Foundation (SNSF), Cancer Council Western Australia (CCWA), National Health and Medical Research Council (NHMRC) |
| Projects and Grants: | MGS T1-BIO-1854, MC AMAROUT Fellow, CCWA Suzanne Cavanagh Early Career Investigator Grant, NHMRC Principal Research Fellowship, NHMRC APP1072113, NHMRC Early Career Fellowship |
| Date Deposited: | 13 Feb 2019 00:14 |
| FoR Codes: | 32 BIOMEDICAL AND CLINICAL SCIENCES > 3204 Immunology > 320404 Cellular immunology @ 100% |
| SEO Codes: | 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920199 Clinical Health (Organs, Diseases and Abnormal Conditions) not elsewhere classified @ 100% |
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