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.
Subject(s)
Antineoplastic Agents/pharmacology , Breast Neoplasms , Lipoproteins/pharmacology , Oncogene Protein v-akt/metabolism , Phosphatidylinositol 3-Kinase/metabolism , Phospholipase A2 Inhibitors/pharmacology , Antineoplastic Agents/isolation & purification , Cell Adhesion/drug effects , Cell Line, Tumor , Cell Movement/drug effects , Cell Survival/drug effects , Crotalid Venoms/chemistry , Endothelial Cells/drug effects , Humans , Lipoproteins/isolation & purification , Models, Biological , Neovascularization, Pathologic , Phospholipase A2 Inhibitors/isolation & purificationABSTRACT
Phospholipases A(2) (PLA(2)s) overexpression is closely associated with the malignant potential of breast cancers. Here, we showed for the first the antitumoral effects of gamma CdcPLI, a PLA2 inhibitor from Crotalus durissus collilineatus via PI3K/Akt pathway on MDA-MB-231 cell. Firstly, gamma CdcPLI 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, gamma CdcPLI induced modulation of important mediators of apoptosis pathways such as p53, MAPK-ERK, BIRC5 and MDM2.gamma CdcPLI decreased MDA-MB-231 adhesion, migration and invasion. Interestingly, the gamma CdcPLI 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,gamma CdcPLI reduced the production of vascular endothelial growth factor (VEGF).gamma CdcPLI was also able to decrease PGE2 levels in MDA-MB-231 and inhibited gene and protein expression of the PI3K/Akt pathway. In conclusion,gamma CdcPLI showed in vitro antitumoral, antimestatatic and anti-angiogenic potential effects and could be an attractive approach for futures studies in cancer therapy.
