Genotoxic effects of BnSP-6, a Lys-49 phospholipase A(2) (PLA(2)) homologue from Bothrops pauloensis snake venom, on MDA-MB-231 breast cancer cells

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Silva, Makswell Almeida ; Lopes, Daiana Silva ; Teixeira, Samuel Cota ; Cirilo Gimenes, Sarah Natalie ; Vasconcelos Azevedo, Fernanda Van Petten ; Polloni, Lorena ; Borges, Bruna Cristina ; da Silva, Marcelo Santos ; Barbosa, Marcelo Jose ; de Oliveira Junior, Robson Jose ; Elias, Maria Carolina ; da Silva, Claudio Vieira ; Geraldo Yoneyama, Kelly Aparecida ; Rodrigues, Veridiana de Melo ; Rodrigues, Renata Santos

• Document type: Journal article
• Source: International Journal of Biological Macromolecules; v. 118, p. 9-pg., 2018-10-15.

Abstract

Herein we evaluated the genotoxic effects of BnSP-6, a Lys-49 phospholipase A(2) (PLA(2)) from Bothrops pauloensis, on breast cancer cells. BnSP-6 was able to induce a higher cytotoxic and genotoxic activity in MDA-MB-231 cells, when compared to MCF10A (a non-tumorigenic breast cell line), suggesting that this protein presented a possible preference for cancer cells. BnSP-6 inhibited MDA-MB-231 proliferation at 24, 48 and 72 h. In addition, BnSP-6 induced significant increase in the percentage of TUNEL-positive cells, a marker of DNA damage. To obtain novel insight into the direct DNA damage interference in MDA-MB-231 survival and proliferation, we evaluated cell cycle progression. BnSP-6 produced a significant decrease in 2N (GI) and an increase in the G2/M phase and this capacity is likely related to the modulation of expression of progression cell cycle-associated genes (CCND1, CCNE1, CDC25A, CHEK2, E2F1, CDH-1 and NF-kB). Taken together, these results indicate that BnSP-6 induces DNA damage in breast cancer cells and is an attractive model for developing innovative therapeutic agents against breast cancer. (C) 2018 Elsevier B.V. All rights reserved. (AU)

• FAPESP's process: 13/07467-1 - CeTICS - Center of Toxins, Immune-Response and Cell Signaling
• Grantee: Hugo Aguirre Armelin
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 14/24170-5 - DNA replication dynamics in Trypanosoma cruzi: licensing and replication rate characterization
• Grantee: Marcelo Santos da Silva
• Support Opportunities: Scholarships in Brazil - Post-Doctoral