Akt, COX-2, RUNX1 and MMPs expression in metastatic melanomas and Biotechnology prospection of molecules with antineoplastic activity

Abstract

Melanoma is a neoplasm derived of melanocytes that is associated with aggressive clinical behavior and mainly by the high propensity for metastatic spread, which results in a poor prognosis. Several molecules have been identified as having important roles to play in invasion and metastasis processes. Akt is associated with cell survival, metabolism regulation, migration and apoptosis. Recent studies reported that transcription factor RUNX1 activates the PI3K signaling pathway, resulting in phosphorylation of Akt, on the other hand, the cells showed inhibition of migration, apoptosis and invasion when Akt is silencing in vitro in many cells of different tumors. In cancer cells, Akt is also believed to be upregulated by the COX-2 pathway and is associated with a more aggressive phenotype in tumors, including by activation of metalloproteinases matrix, especially MMP-2 and MMP -9. Bioactive compounds derived from natural products are studied for their potential antitumour, and biotechnological prospecting of plant extracts are promising options for cancer treatment. Thus, the project aims to: (1) study the relationship of signaling pathways (Akt, COX-2, RUNX1 and MMPs) in metastasis progression of melanoma model in vivo and in vitro, and (2) evaluate the effect of the extracts, fractions and bioproducts of Croton cajucara Benth in microemulsion systems in melanoma cells. In vitro and in vivo studies shall be proposed. In vitro model will be evaluated the expression of proteins in human melanoma cell lines treated or not. In the in vivo model, mice will be submitted to the application of B16F10 cells in tongue for metastasis induction and treated with Croton cajucara. Histological analysis will be performed, immunohistochemistry and WB to assess antineoplastic and antimetastatic effects of bioactive compounds.