{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T04:05:34Z","timestamp":1783569934587,"version":"3.55.0"},"reference-count":35,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,2,14]],"date-time":"2021-02-14T00:00:00Z","timestamp":1613260800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Regional Madrid Government","award":["2018-T1\/BIO-11262"],"award-info":[{"award-number":["2018-T1\/BIO-11262"]}]},{"DOI":"10.13039\/100011264","name":"FP7 People: Marie-Curie Actions","doi-asserted-by":"publisher","award":["N 291803-AMAROUT II"],"award-info":[{"award-number":["N 291803-AMAROUT II"]}],"id":[{"id":"10.13039\/100011264","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Melanoma is the main cause of skin cancer deaths, with special emphasis in those cases carrying BRAF mutations that trigger the mitogen-activated protein kinases (MAPK) signaling and unrestrained cell proliferation in the absence of mitogens. Current therapies targeting MAPK are hindered by drug resistance and relapse that rely on metabolic rewiring and Akt activation. To identify new drug candidates against melanoma, we investigated the molecular mechanism of action of the Octopus Kaurna-derived peptide, Octpep-1, in human BRAF(V600E) melanoma cells using proteomics and RNAseq coupled with metabolic analysis. Fluorescence microscopy verified that Octpep-1 tagged with fluorescein enters MM96L and NFF cells and distributes preferentially in the perinuclear area of MM96L cells. Proteomics and RNAseq revealed that Octpep-1 targets PI3K\/AKT\/mTOR signaling in MM96L cells. In addition, Octpep-1 combined with rapamycin (mTORC1 inhibitor) or LY3214996 (ERK1\/2 inhibitor) augmented the cytotoxicity against BRAF(V600E) melanoma cells in comparison with the inhibitors or Octpep-1 alone. Octpep-1-treated MM96L cells displayed reduced glycolysis and mitochondrial respiration when combined with LY3214996. Altogether these data support Octpep-1 as an optimal candidate in combination therapies for melanoma BRAF(V600E) mutations.<\/jats:p>","DOI":"10.3390\/toxins13020146","type":"journal-article","created":{"date-parts":[[2021,2,14]],"date-time":"2021-02-14T10:01:05Z","timestamp":1613296865000},"page":"146","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["ERK and mTORC1 Inhibitors Enhance the Anti-Cancer Capacity of the Octpep-1 Venom-Derived Peptide in Melanoma BRAF(V600E) Mutations"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8602-8554","authenticated-orcid":false,"given":"Javier","family":"Moral-Sanz","sequence":"first","affiliation":[{"name":"Translational Venomics Group, Madrid Institute for Advanced Studies in Food, E28049 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel A.","family":"Fernandez-Rojo","sequence":"additional","affiliation":[{"name":"Hepatic Regenerative Medicine Group, Madrid Institute for Advanced Studies in Food, E28049 Madrid, Spain"},{"name":"Diamantina Institute, The University of Queensland, Brisbane, QLD 4072, Australia"},{"name":"Department of Cell and Molecular Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy","family":"Potriquet","sequence":"additional","affiliation":[{"name":"Infectious Diseases Program, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia"},{"name":"AB SCIEX, 2 Gilda Court, Mulgrave, Melbourne, VIC 3170, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela","family":"Mukhopadhyay","sequence":"additional","affiliation":[{"name":"Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Brust","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Wilhelm","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2211-0265","authenticated-orcid":false,"given":"Taylor B.","family":"Smallwood","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, The University of Queensland, Brisbane, QLD 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6807-5426","authenticated-orcid":false,"given":"Richard J.","family":"Clark","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia"},{"name":"School of Biomedical Sciences, The University of Queensland, Brisbane, QLD 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6661-1283","authenticated-orcid":false,"given":"Bryan G.","family":"Fry","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, The University of Queensland, Brisbane, QLD 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul F.","family":"Alewood","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Waddell","sequence":"additional","affiliation":[{"name":"Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5506-6304","authenticated-orcid":false,"given":"John J.","family":"Miles","sequence":"additional","affiliation":[{"name":"Department of Immunology, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia"},{"name":"The Australian Institute of Tropical Health and Medicine (AITHM), James Cook University, Cairns, QLD 4811, Australia"},{"name":"Centre for Molecular Therapeutics, James Cook University, Cairns, QLD 4811, Australia"},{"name":"Centre for Tropical Bioinformatics and Molecular Biology, James Cook University, Cairns, QLD 4811, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason P.","family":"Mulvenna","sequence":"additional","affiliation":[{"name":"Infectious Diseases Program, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7739-080X","authenticated-orcid":false,"given":"Maria P.","family":"Ikonomopoulou","sequence":"additional","affiliation":[{"name":"Translational Venomics Group, Madrid Institute for Advanced Studies in Food, E28049 Madrid, Spain"},{"name":"Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia"},{"name":"Department of Immunology, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1038\/nature00766","article-title":"Mutations of the BRAF gene in human 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