A novel antitumor WT1-derived peptide: anti-melanoma activity and mechanisms of action

• Grant number: 12/19476-2
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: May 01, 2013
• End date: August 10, 2014
• Field of knowledge: Biological Sciences - Biology
• Principal Investigator: Luiz Rodolpho Raja Gabaglia Travassos
• Grantee: Mariana Hiromi de Souza Massaoka
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

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.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

MASSAOKA, MARIANA H.; MATSUO, ALISSON L.; FIGUEIREDO, CARLOS R.; GIROLA, NATALIA; FARIA, CAMYLA F.; AZEVEDO, RICARDO A.; TRAVASSOS, LUIZ R.. A novel cell-penetrating peptide derived from WT1 enhances p53 activity, induces cell senescence and displays antimelanoma activity in xeno- and syngeneic systems. FEBS OPEN BIO, v. 4, p. 153-161, 2014. (12/19476-2, 10/51423-0)