PLP2-derived peptide Rb4 triggers PARP-1-mediated necrotic death in murine melanoma cells

Author(s)

Maia, Vera S. C. ; Berzaghi, Rodrigo ; Arruda, Denise C. ; Machado, Fabricio C. ; Loureiro, Leticia L. ; Melo, Pollyana M. S. ; Morais, Alice S. ; Budu, Alexandre ; Travassos, Luiz R.

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 12, n. 1, p. 13-pg., 2022-02-21.

Abstract

Malignant melanoma is the main cause of death in patients with skin cancer. Overexpression of Proteolipid protein 2 (PLP2) increased tumor metastasis and the knockdown of PLP2 inhibited the growth and metastasis of melanoma cells. In the present work, we studied the antitumor activity of peptide Rb4 derived from protein PLP2. In vitro, Rb4 induced F-actin polymerization, prevented F-actin depolymerization and increased the ER-derived cytosolic calcium. Such effects were associated with necrosis of murine melanoma B16F10-Nex2 cells and with inhibition of the viability of human cancer cell lines. Loss of plasma membrane integrity, dilation of mitochondria, cytoplasm vacuolation and absence of chromatin condensation characterized tumor cell necrosis. Cleavage of PARP-1 and inhibition of RIP1 expression were also observed. In vivo, peptide Rb4 reduced the lung metastasis of tumor cells and delayed the subcutaneous melanoma growth in a syngeneic model. Rb4 induced the expression of two DAMPs molecules, HMGB1 and calreticulin, in B16F10-Nex2. Our results suggest that peptide Rb4 acts directly on tumor cells inducing the expression of DAMPs, which trigger the immunoprotective effect in vivo against melanoma cells. We suggest that peptide Rb4 is a promising compound to be developed as an anticancer drug. (AU)

• FAPESP's process: 10/51423-0 - Bioactive peptides and peptidases: biological and immunobiological activities in infectious diseases and cancer
• Grantee: Luiz Rodolpho Raja Gabaglia Travassos
• Support Opportunities: Research Projects - Thematic Grants