Human breast cancer cell death induced by BnSP-6, a Lys-49 PLA₂ homologue from Bothrops pauloensis venom.

Abstract

This work shows the antitumoral effects of BnSP-6, a Lys 49 PLA2 isolated from Bothrops pauloensis venom, on human breast cancer MDA-MB-231 cells. BnSP-6 caused a dose-dependent cytotoxicity and inhibited cell adhesion. Interestingly, cytotoxic activity of BnSP-6 was significantly lower against MCF10A, a non-tumorigenic breast cell line, suggesting that this PLA2 presented a possible preference for targets in cancer cells. Analysis of cell death on MDA-MB-231 cells showed that BnSP-6 stimulated the autophagy process, as evidenced by labeling of autophagic vacuoles. Moreover, apoptosis assays showed that BnSP-6 induced both early and late apoptosis. Apoptosis of MDA-MB-231 cells was also confirmed by up-regulation of different genes related to the apoptosis pathway, such as TNF, TNFRSF10B, TNFRSF1A and CASP8 and decreased expression of anti-apoptotic genes (BCL2 and BCL2L). In addition, BnSP-6 caused a remarkable increase in gene expression of BRCA2 and TP53 tumor suppressors. Finally, BnSP-6 induced down-regulation of Angiopoetin 1 gene (potent pro-angiogenic factor) and inhibited adhesion and migration of MDA-MB-231 cells suggesting pharmaceutical applications of this PLA2 as an antiangiogenic and anti-metastatic agent. Taken together, our results show that the PLA2 BnSP-6 presents anticancer potential that can be exploited as prototype for the design of new therapies.

• Authors: Fernanda Van Petten Vasconcelos Azevedo, Daiana Silva Lopes, Sarah Natalie Cirilo Gimenes, David Collares Achê, Lara Vecchi, Patrícia Terra Alves, Denise de Oliveira Guimarães, Renata Santos Rodrigues, Luiz Ricardo Goulart, Veridiana de Melo Rodrigues, Kelly Aparecida Geraldo Yoneyama
• Journal: International journal of biological macromolecules (Int J Biol Macromol) Vol. 82 Pg. 671-7 (Jan 2016) ISSN: 1879-0003 [Electronic] Netherlands
• PMID: 26519876 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• Crotalid Venoms
• BnSP-6
• Phospholipases A2

Topics

• Animals
• Apoptosis (drug effects)
• Autophagy (drug effects)
• Bothrops (metabolism)
• Breast Neoplasms
• Cell Adhesion (drug effects)
• Cell Death (drug effects)
• Cell Line, Tumor
• Cell Movement
• Crotalid Venoms (chemistry, isolation & purification, toxicity)
• Female
• Gene Expression
• Humans
• Phospholipases A2 (chemistry, isolation & purification, toxicity)
• Protein Interaction Domains and Motifs