Back to Search Start Over

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

Authors :
Fernandez-Rojo MA
Deplazes E
Pineda SS
Brust A
Marth T
Wilhelm P
Martel N
Ramm GA
Mancera RL
Alewood PF
Woods GM
Belov K
Miles JJ
King GF
Ikonomopoulou MP
Source :
Cell death discovery [Cell Death Discov] 2018 Feb 14; Vol. 4, pp. 19. Date of Electronic Publication: 2018 Feb 14 (Print Publication: 2018).
Publication Year :
2018

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.<br />Competing Interests: The authors declare that they have no conflict of interest.

Details

Language :
English
ISSN :
2058-7716
Volume :
4
Database :
MEDLINE
Journal :
Cell death discovery
Publication Type :
Academic Journal
Accession number :
29531816
Full Text :
https://doi.org/10.1038/s41420-018-0030-0