Genotoxic effects of BnSP-6, a Lys-49 phospholipase A2 (PLA2) homologue from Bothrops pauloensis snake venom, on MDA-MB-231 breast cancer cells
Silva, Makswell Ferreira S.; Lopes, Daiana Silva; Teixeira, Samuel Cota; Gimenes, Sarah Natalie Cirilo ; Azevedo, Fernanda Van Petten Vasconcelos; Polloni, Lorena; Borges, Bruna Cristina; Silva, Marcelo Santos da ; Barbosa, Marcelo José; Oliveira Júnior, Robson José de; Elias, Maria Carolina ; Da Silva, Cláudio Vieira; Yoneyama, Kelly Aparecida Geraldo; Rodrigues, Veridiana De Melo; Rodrigues, Renata Santos
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.
PLA2; BnSP-6; Breast cancer; Genotoxicity; Cell cycle; Bothrops pauloensis
Silva MFS., Lopes DS, Teixeira SC, Gimenes SNC, Azevedo FVPV, Polloni L, et al. Genotoxic effects of BnSP-6, a Lys-49 phospholipase A2 (PLA2) homologue from Bothrops pauloensis snake venom, on MDA-MB-231 breast cancer cells. Int. J. Biol. Macromol.. 2018 Oct;118(part A):311-9. doi:10.1016/j.ijbiomac.2018.06.082.
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