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Genotoxic effects of BnSP-6, a Lys-49 phospholipase A2 (PLA2) homologue from Bothrops pauloensis snake venom, on MDA-MB-231 breast cancer cells. 2018
Makswell Almeida Silva, and
Daiana Silva Lopes, and
Samuel Cota Teixeira, and
Sarah Natalie Cirilo Gimenes, and
Fernanda Van Petten Vasconcelos Azevedo, and
Lorena Polloni, and
Bruna Cristina Borges, and
Marcelo Santos da Silva, and
Marcelo José Barbosa, and
Robson José de Oliveira Júnior, and
Maria Carolina Elias, and
Claudio Vieira da Silva, and
Kelly Aparecida Geraldo Yoneyama, and
Veridiana de Melo Rodrigues, and
Renata Santos Rodrigues
Laboratory of Biochemistry and Animal Toxins, Institute of Biotechnology, Federal University of Uberlandia, UFU, Uberlandia, MG, Brazil.
Herein we evaluated the genotoxic effects of BnSP-6, a Lys-49 phospholipase A2 (PLA2) 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 (G1) 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.
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