PUBLICATION
Gomesin inhibits melanoma growth by manipulating key signaling cascades that control cell death and proliferation
- Authors
- Ikonomopoulou, M.P., Fernandez-Rojo, M.A., Pineda, S.S., Cabezas-Sainz, P., Winnen, B., Morales, R.A.V., Brust, A., Sánchez, L., Alewood, P.F., Ramm, G.A., Miles, J.J., King, G.F.
- ID
- ZDB-PUB-180803-1
- Date
- 2018
- Source
- Scientific Reports 8: 11519 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Antimicrobial Cationic Peptides/pharmacology*
- Antineoplastic Agents/pharmacology*
- Cell Death/drug effects*
- Cell Line, Tumor
- Cell Proliferation/drug effects*
- Disease Models, Animal
- Dose-Response Relationship, Drug
- Heterografts
- Melanoma/drug therapy*
- Mice
- Neoplasm Transplantation
- Signal Transduction/drug effects*
- Treatment Outcome
- Zebrafish
- PubMed
- 30068931 Full text @ Sci. Rep.
Citation
Ikonomopoulou, M.P., Fernandez-Rojo, M.A., Pineda, S.S., Cabezas-Sainz, P., Winnen, B., Morales, R.A.V., Brust, A., Sánchez, L., Alewood, P.F., Ramm, G.A., Miles, J.J., King, G.F. (2018) Gomesin inhibits melanoma growth by manipulating key signaling cascades that control cell death and proliferation. Scientific Reports. 8:11519.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping