Abstract

-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.

Authors	Moral-Sanz, Javier; Fernandez-Rojo, Manuel A; Potriquet, Jeremy; Mukhopadhyay, Pamela; Brust, Andreas; Wilhelm, Patrick; Smallwood, Taylor B; Clark, Richard J; Fry, Bryan G; Alewood, Paul F; Waddell, Nicola; Miles, John J; Mulvenna, Jason P; Ikonomopoulou, Maria P
Journal	Toxins
Pages
Volume	13
Date	1/01/2021
Grant ID
Funding Body
URL	http://www.ncbi.nlm.nih.gov/pubmed/?term=10.3390/toxins13020146