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Antitumoral effects of γCdcPLI, a PLA2 inhibitor from Crotalus durissus collilineatus via PI3K/Akt pathway on MDA-MB-231 breast cancer cell

2017; Nature Portfolio; Volume: 7; Issue: 1 Linguagem: Inglês

10.1038/s41598-017-07082-2

ISSN

2045-2322

Autores

Sarah Natalie Cirilo Gimenes, Daiana Silva Lopes, Patrícia Terra Alves, Fernanda Van Petten de Vasconcelos Azevedo, Lara Vecchi, Luíz Ricardo Goulart, Thaís Carneiro Santos Rodrigues, André Luíz Quagliatto Santos, Vera Lúcia de Campos Brites, Thaíse Lara Teixeira, Cláudio Vieira da Silva, Matheus Henrique Dias, Samuel Cota Teixeira, Renata Santos Rodrigues, Kelly Aparecida Geraldo Yoneyama, Ricardo A. Oliveira, Veridiana de Melo Rodrigues,

Tópico(s)

Mechanisms of cancer metastasis

Resumo

Phospholipases A2 (PLA2s) overexpression is closely associated with the malignant potential of breast cancers. Here, we showed for the first the antitumoral effects of γCdcPLI, a PLA2 inhibitor from Crotalus durissus collilineatus via PI3K/Akt pathway on MDA-MB-231 cell. Firstly, γCdcPLI was more cytotoxic to MDA-MB-231 breast cancer cells than other cell lines (MCF-7, HeLa, PC3 and A549) and did not affect the viability of non-tumorigenic breast cell (MCF 10A). In addition, γCdcPLI induced modulation of important mediators of apoptosis pathways such as p53, MAPK-ERK, BIRC5 and MDM2. γCdcPLI decreased MDA-MB-231 adhesion, migration and invasion. Interestingly, the γCdcPLI also inhibited the adhesion and migration of endothelial cells and blocked angiogenesis by inhibiting tube formation by HUVECs in vitro and sprouting elongation on aortic ring assay ex vivo. Furthermore, γCdcPLI reduced the production of vascular endothelial growth factor (VEGF). γCdcPLI was also able to decrease PGE2 levels in MDA-MB-231 and inhibited gene and protein expression of the PI3K/Akt pathway. In conclusion, γCdcPLI showed in vitro antitumoral, antimestatatic and anti-angiogenic potential effects and could be an attractive approach for futures studies in cancer therapy.

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