Gomesin inhibits melanoma growth by manipulating key signaling cascades that control cell death and proliferation View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-12

AUTHORS

Maria P. Ikonomopoulou, Manuel A. Fernandez-Rojo, Sandy S. Pineda, Pablo Cabezas-Sainz, Brit Winnen, Rodrigo A. V. Morales, Andreas Brust, Laura Sánchez, Paul F. Alewood, Grant A. Ramm, John J. Miles, Glenn F. King

ABSTRACT

Consistent with their diverse pharmacology, peptides derived from venomous animals have been developed as drugs to treat disorders as diverse as hypertension, diabetes and chronic pain. Melanoma has a poor prognosis due in part to its metastatic capacity, warranting further development of novel targeted therapies. This prompted us to examine the anti-melanoma activity of the spider peptides gomesin (AgGom) and a gomesin-like homolog (HiGom). AgGom and HiGom dose-dependently reduced the viability and proliferation of melanoma cells whereas it had no deleterious effects on non-transformed neonatal foreskin fibroblasts. Concordantly, gomesin-treated melanoma cells showed a reduced G0/G1 cell population. AgGom and HiGom compromised proliferation of melanoma cells via activation of the p53/p21 cell cycle check-point axis and the Hippo signaling cascade, together with attenuation of the MAP kinase pathway. We show that both gomesin peptides exhibit antitumoral activity in melanoma AVATAR-zebrafish xenograft tumors and that HiGom also reduces tumour progression in a melanoma xenograft mouse model. Taken together, our data highlight the potential of gomesin for development as a novel melanoma-targeted therapy. More... »

PAGES

11519

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41598-018-29826-4

DOI

http://dx.doi.org/10.1038/s41598-018-29826-4

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1105858710

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30068931


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