Angiotensin 1-7 modulates molecular and cellular processes central to the pathogenesis of prostate cancer.

Angiotensin 1-7 (Ang1-7) is an endogenous bioactive component of the renin-angiotensin system (RAS). In addition to its cardiovascular properties, its anti-proliferative and anti-angiogenic traits are believed to play important roles in carcinogenesis. The present study examines the influence of Ang1-7 on processes associated with development and progression of prostate cancer cells. Our findings indicate that while Ang1-7 (1 nM; 48 h) can effectively reduce cell proliferation in DU-145, it can induce a significant decrease in the expression of MKI67 in LNCaP. In both cell lines we also observed a reduction in colony size in soft agar assay. A various changes in gene expression were noted after exposure to Ang1-7: those of anti- and pro-apoptotic agents and the NF-kB family of transcription factors, as well as mesenchymal cell markers and vascular endothelial growth factor A (VEGFA). In addition, Ang1-7 was found to modulate cell adhesion and matrix metallopeptidase (MMP) activity. Changes were also observed in the levels of angiotensin receptors and sex steroid hormone receptors. Ang1-7 reduced the levels of estrogen receptor alpha gene (ESR1) and increased the expression of estrogen receptor beta gene (ESR2) in all prostate cancer cells; it also up-regulated androgen receptor (AR) expression in androgen-sensitive cells but contradictory effect was observed in androgen- irresponsive cell lines. In summary, the results confirm the existence of complex network between the various elements of the local RAS and the molecular and cellular mechanisms of prostate cancerogenesis. The response of cancer cells to Ang1-7 appears to vary dependently on the dose and time of incubation as well as the aggressiveness and the hormonal status of cells.

Influence and mechanism of Angiotensin 1-7 on biological properties of normal prostate epithelial cells.

The ACE2/Ang1-7/MAS axis was involved in the cell proliferation, migration and apoptosis of many types of reproductive tissues. The research was conducted on prostate epithelial cells, immortalized by Simian Virus 40. We examined the influence of Ang 1-7 on biological properties of PNT1A cells after 24- or 48-h treatment. The employed selective antagonists of angiotensin receptors allowed evaluation of the receptor mediating Ang1-7 action. Our data clearly indicate that Ang1-7 can decrease cell proliferation and epithelial-to-mesenchymal transition of PNT1A cells via inactivation of PI3K axis and modulation of expression of the NF-kB gene family. Furthermore, it counteracts oxidant stress and inflammation in prostate cells by inhibition of VEGF expression and MMPs activation as well as by modulating the level of ERα and ERß. On the other hand, this heptapeptide can promote cell survival by alteration of expression of anti- and pro-apoptotic members as well as compensatory up-regulation of AR expression. Summary, the results confirm the existence of a complicated dependence networks between the various elements of the local RAS and steroid hormone receptor pathways in prostate gland. Furthermore, shows the chances of using ACE2/Ang1-7/MAS pathway as a novel therapeutic target in prevention and treatment of prostate diseases.

Comparison of leukocyte IL6 expression in patients with gestational diabetes mellitus (GDM) diagnosed by the Polish Diabetes Association (PDA) 2011 and 2014 criteria.

INTRODUCTION: Controversial data exist in the literature regarding relationship of IL-6 with gestational diabetes mellitus (GDM), partially resulting from different criteria for GDM classification. In the present study, we revised this linkage by investigating leukocyte IL6 expression and its associations with clinical characteristics of patients diagnosed by the Polish Diabetes Association (PDA) 2011 and 2014 criteria. MATERIAL AND METHODS: A total of 145 pregnant women underwent 75 g two-hour OGTT, and GDM was diagnosed according to PDA 2011 criteria (GDM/PDA 2011 group; n = 113) and PDA 2014 criteria (GDM/PDA 2014 group; n = 104). IL6 gene expression was investigated in leukocytes of all participants by using real-time PCR method. RESULTS: Compared to respective NGT control groups, the GDM/PDA 2011 group exhibited higher FPG, two-hour OGTT, HbA1C and IL6 expression and lower HDL-C, whereas the GDM/PDA 2014 group had higher FPG, one-hour and two-hour OGTT, HbA1C and HOMA-IR, lower QUICKI-IS, and unchanged IL6 expression. No differences in metabolic parameters and IL6 expression were found between the two GDM groups. Compared to the NGT/PDA 2011 group, the NGT/PDA 2014 group had lower one-hour and higher two-hour OGTT and increased IL6 expression. With PDA 2014 criteria, IL6 expression correlated positively with two-hour OGTT in both NGT and GDM groups as well as with LDL-C in NGT group, and negatively with HDL-C in NGT group. With PDA 2011 criteria, no associations were evident in NGT and GDM groups. Nevertheless, significant positive correlation of IL6 mRNA with two-hour OGTT was observed in the entire study group. CONCLUSIONS: Differences in metabolic phenotypes as well as gene expression and correlation data between GDM and NGT groups, categorised based on PDA 2011 and 2014 criteria, are related to changes in gestational glucose tolerance status resulting from using PDA 2014 criteria. Moreover, our findings support the hypothesis that IL-6 is associated with glucose metabolism during pregnancy.