Antitumoral effects of γCdcPLI, a PLA2 inhibitor from Crotalus durissus collilineatus via PI3K/Akt pathway on MDA-MB-231 breast cancer cell
Abstract 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 wa...
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oai:doaj.org-article:cf5dafde05bf43f6853f2171734ef6452021-12-02T15:04:55ZAntitumoral effects of γCdcPLI, a PLA2 inhibitor from Crotalus durissus collilineatus via PI3K/Akt pathway on MDA-MB-231 breast cancer cell10.1038/s41598-017-07082-22045-2322https://doaj.org/article/cf5dafde05bf43f6853f2171734ef6452017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07082-2https://doaj.org/toc/2045-2322Abstract 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.Sarah N. C. GimenesDaiana S. LopesPatrícia T. AlvesFernanda V. P. V. AzevedoLara VecchiLuiz R. GoulartThais C. S. RodriguesAndré L. Q. SantosVera L. de C. BritesThaise L. TeixeiraCláudio V. da SilvaMatheus H. DiasSamuel C. TeixeiraRenata S. RodriguesKelly A. G. YoneyamaRicardo A. OliveiraVeridiana de M. RodriguesNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017) |
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Medicine R Science Q Sarah N. C. Gimenes Daiana S. Lopes Patrícia T. Alves Fernanda V. P. V. Azevedo Lara Vecchi Luiz R. Goulart Thais C. S. Rodrigues André L. Q. Santos Vera L. de C. Brites Thaise L. Teixeira Cláudio V. da Silva Matheus H. Dias Samuel C. Teixeira Renata S. Rodrigues Kelly A. G. Yoneyama Ricardo A. Oliveira Veridiana de M. Rodrigues Antitumoral effects of γCdcPLI, a PLA2 inhibitor from Crotalus durissus collilineatus via PI3K/Akt pathway on MDA-MB-231 breast cancer cell |
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Abstract 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. |
format |
article |
author |
Sarah N. C. Gimenes Daiana S. Lopes Patrícia T. Alves Fernanda V. P. V. Azevedo Lara Vecchi Luiz R. Goulart Thais C. S. Rodrigues André L. Q. Santos Vera L. de C. Brites Thaise L. Teixeira Cláudio V. da Silva Matheus H. Dias Samuel C. Teixeira Renata S. Rodrigues Kelly A. G. Yoneyama Ricardo A. Oliveira Veridiana de M. Rodrigues |
author_facet |
Sarah N. C. Gimenes Daiana S. Lopes Patrícia T. Alves Fernanda V. P. V. Azevedo Lara Vecchi Luiz R. Goulart Thais C. S. Rodrigues André L. Q. Santos Vera L. de C. Brites Thaise L. Teixeira Cláudio V. da Silva Matheus H. Dias Samuel C. Teixeira Renata S. Rodrigues Kelly A. G. Yoneyama Ricardo A. Oliveira Veridiana de M. Rodrigues |
author_sort |
Sarah N. C. Gimenes |
title |
Antitumoral effects of γCdcPLI, a PLA2 inhibitor from Crotalus durissus collilineatus via PI3K/Akt pathway on MDA-MB-231 breast cancer cell |
title_short |
Antitumoral effects of γCdcPLI, a PLA2 inhibitor from Crotalus durissus collilineatus via PI3K/Akt pathway on MDA-MB-231 breast cancer cell |
title_full |
Antitumoral effects of γCdcPLI, a PLA2 inhibitor from Crotalus durissus collilineatus via PI3K/Akt pathway on MDA-MB-231 breast cancer cell |
title_fullStr |
Antitumoral effects of γCdcPLI, a PLA2 inhibitor from Crotalus durissus collilineatus via PI3K/Akt pathway on MDA-MB-231 breast cancer cell |
title_full_unstemmed |
Antitumoral effects of γCdcPLI, a PLA2 inhibitor from Crotalus durissus collilineatus via PI3K/Akt pathway on MDA-MB-231 breast cancer cell |
title_sort |
antitumoral effects of γcdcpli, a pla2 inhibitor from crotalus durissus collilineatus via pi3k/akt pathway on mda-mb-231 breast cancer cell |
publisher |
Nature Portfolio |
publishDate |
2017 |
url |
https://doaj.org/article/cf5dafde05bf43f6853f2171734ef645 |
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