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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Autores principales: 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
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spelling 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)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle 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
description 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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