The Experimental Oncology Unit (UNONEX) aims innovative therapies for the treatment of malignant melanoma and has been mainly focused on bioactive peptides from various sources (Dobroff et al., 2002, 2010; Polonelli et al., 2008; Matsuo, 2011; Arruda et al, 2012). We have shown that a lysine-arginine rich peptide (WT1-pTj) based on WT1 C-terminal zinc finger domain was able to inhibit melanoma cells proliferation, as well as the replication of other WT1-expressing cancer cell lines. Our previous results suggest cell cycle arrest in the G2 / M phase, induction of senescence and autophagy, and decrease in clonogenic ability of A2058 human melanoma cells after treatment with WT1-pTj. It has been demonstrated that the peptide entered the cell within 15 minutes and was diffusely distributed throughout the cell, including the nucleus, pointing the cell-penetrating feature of WT1-pTj. In vivo, WT1 pTj reduced the number of lung nodules in the B16F10-Nex2 syngeneic model of metastatic melanoma and prolonged survival of mice in the A2058 subcutaneous xenograft model. Therefore, this Project aims to characterize the activity of WT1-pTj as a novel Trojan peptide that displays antitumor effect using in vitro and in vivo systems of murine (B16F10-Nex2) and human (A2058) melanoma, and defining the mechanisms of action, distribution and targeting.
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