In:
Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 68, No. suppl_1 ( 2016-09)
Abstract:
Previously studies have demonstrated that besides its actions in the cardiovascular system, Angiotensin-(1-7) also plays a role in inhibiting tumoral growth. The role of recently described Alamandine in this field is not clear. The signaling pathways underling anti-tumoral actions of these peptides are also poorly understood. Therefore, the aim of this study was to elucidate the modulatory effect of Ang-(1-7) and Alamandine in the PI3K cascade, a well-known signaling pathway described to be involved in proliferation and cancer. To achieve this goal, we stimulate human pancreatic and lung cancer cell lineage (Miapaca and A549), as well as a control cell lineage (VERO) with Ang-(1-7) and Alamandine. Through western blotting analysis, our data suggest that both Ang-(1-7) and Alamandine activate the phosphatase pTEN (dephosphorylation of S380/T382/T383) (48±4% after 24 hours Ang-(1-7) treatment in miapaca and A549 in comparison of non-treated cells, p 〈 0.05) (60±5 and 48±4% of phosphorylation level after 24 hours Alamandine treatment in miapaca and A549, respectively, in comparison of non-treated cells, p 〈 0.05), which dephosphorylates PI3K, inactivating this kinase. Furthermore, AKT phosphorylation is transient, followed by a significant dephosphorylation when compared to the non-treated cells (30±5% after 24 hours Ang-(1-7) treatment in miapaca in comparison of non-treated cells, p 〈 0.05). Ang-(1-7) also inhibits a PTEN downstream effector kinase, mTOR through dephosphorylation of T246 (70±5% after 24 hours Ang-(1-7) treatment in miapaca in comparison of non-treated cells, p 〈 0.05). These effects were not observed in control non-tumoral cells (VERO cells). As previously demonstrated with Ang-(1-7) stimulation, Alamandine also induces the FOXO1 activation and migration to the nucleus in A549 (122 ± 8 of A.U. of fluorescence at 4 hours after alamandine treatment vs 46±4 A.U. at control, p 〈 0.001) and Miapaca cells (67 ± 5 of A.U. of fluorescence at 4 hours after alamandine treatment vs 16±2 A.U. at control, p 〈 0.001). These results indicate that, in contrast to normal tissues, Ang-(1-7) and Alamandine decreases, through PTEN activation, PI3K/AKT pathway in tumoral cells.
Type of Medium:
Online Resource
ISSN:
0194-911X
,
1524-4563
DOI:
10.1161/hyp.68.suppl_1.p102
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2016
detail.hit.zdb_id:
2094210-2
