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

Ikonomopoulou, Maria P., Fernandez-Rojo, Manuel A., Pineda, Sandy S., Cabezas-Sainz, Pablo, Winnen, Brit, Morales, Rodrigo A.V., Brust, Andreas, Sánchez, Laura, Alewood, Paul F., Ramm, Grant A., Miles, John, and King, Glenn F. (2018) Gomesin inhibits melanoma growth by manipulating key signaling cascades that control cell death and proliferation. Scientific Reports, 8.

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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.

Item ID: 56635
Item Type: Article (Research - C1)
ISSN: 2045-2322
Copyright Information: 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/licenses/by/4.0/.
Funders: Perpetual, Australian Research Council (ARC), Queensland Institute of Medical Research (QIMR), Madrid Government of Spain (MGS), National Health and Medical Research Council (NHMRC)
Projects and Grants: Perpetual IMPACT IDIPAP2015/1585, ARC DP1095728, ARC DP130103813, MGS T1-BIO-1854, NHMRC APP1131732, NHMRC APP1136889
Date Deposited: 11 Jan 2019 04:39
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110799 Immunology not elsewhere classified @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920102 Cancer and Related Disorders @ 100%
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