Abstract 2701: Antitumor effects of peptide Rb4 derived from proteolipid protein 2 (PLP2) in a syngeneic murine melanoma model

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Peptides have increasingly being investigated as drug candidates for treatment of pathologies ranging from Alzheimer`s disease to cancer. Literature shows that over expression of proteolipid protein 2 (PLP2) was associated with metastasis of B16F10 melanoma. Authors showed later that knock-down of PLP2 inhibited growth and metastasis of melanoma cells. The present work aimed at studying the antitumor activity of peptide Rb4 derived from protein PLP2. Peptide Rb4, tested as synthetic peptide on B16F10-Nex2 cells showed antitumor effects in vitro and in vivo. Rb4 induces a remarkable F-actin depolymerization, and also antagonizes thapsigargin blockade of calcium channels on the endoplasmic reticulum (ER). Such effects on actin dynamics and calcium flow cause apoptosis in murine melanoma B16F10-Nex2, and reduce the viability of several human cancer cell lines. Chromatin condensation, DNA fragmentation, caspase 9 and caspase 3 activation are compatible with tumor cell apoptosis. Early effects of the peptide were cell rounding and aggregation, followed by substrate detachment. In vivo, peptide Rb4 reduced metastatic activity of B16F10-Nex2 cells and delayed the subcutaneous growth of murine melanoma in the syngeneic model. The protective effect of Rb4 observed in the metastatic melanoma model was not, however, observed in immunodeficient mice. Peptide Rb4 induces the expression of two DAMPs (damage-associated molecular patterns), HMGB1 and calreticulin in B16F10-Nex2. Apart from a direct adjuvant effect of Rb4 on dendritic cells (DCs), the expression of DAMPs by tumor cells may also contribute to DCs activation thus explaining the protective effect of the peptide in vivo against B16F10-Nex2 melanoma. In conclusion, we suggest that peptide Rb4 is a promising compound to be developed as an anticancer drug. Supported by FAPESP grant 2010/51423-0 and the Brazilian National Research Council (CNPq). Citation Format: Vera S C Maia, Rodrigo Berzaghi, Denise C. Arruda, Pollyana M S Melo, Luiz R. Travassos. Antitumor effects of peptide Rb4 derived from proteolipid protein 2 (PLP2) in a syngeneic murine melanoma model. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2701. doi:10.1158/1538-7445.AM2014-2701