Gomesin inhibits melanoma growth by manipulating key signaling cascades that control cell death and proliferation.
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| 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.
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| 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 |
| Journal | Scientific reports (Sci Rep) Vol. 8 Issue 1 Pg. 11519 (08 01 2018) ISSN: 2045-2322 [Electronic] England |
| PMID | 30068931 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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