Role of IAPs in prostate cancer progression: immunohistochemical study in normal and pathological (benign hyperplastic, prostatic intraepithelial neoplasia and cancer) human prostate

<p>Abstract</p> <p>Background</p> <p>In this study was investigate IAPs in normal human prostate (NP), benign prostatic hyperplasia (BPH), prostatic intraepithelial neoplasia (PIN) and prostatic carcinoma (PC), and their involvement in apoptosis/proliferation via NF-kB (TNF-α, IL-1) stimulation.</p> <p>Methods</p> <p>Immunohistochemical and Western blot analyses were performed in 10 samples of normal prostates, 35 samples of BPH, 27 samples diagnosis of PIN (with low-grade PIN or high-grade PIN) and 95 samples of PC (with low, medium or high Gleason grades).</p> <p>Results</p> <p>In NP, cytoplasm of epithelial cells were positive to c-IAP1/2 (80% of samples), c-IAP-2 (60%), ILP (20%), XIAP (20%); negative to NAIP and survivin. In BPH, epithelial cells were immunostained to c-IAP1/2 (57.57%), c-IAP-2 (57.57%), ILP (66.6%), NAIP (60.6%), XIAP (27.27%), survivin (9.1%). Whereas low-grade PIN showed intermediate results between NP and BPH; results in high-grade PIN were similar to those found in PC. In PC, epithelial cells were immunostained to c-IAP1/2, c-IAP-2, ILP, NAIP, XIAP (no Gleason variation) and survivin (increasing with Gleason).</p> <p>Conclusions</p> <p>IAPs could be involved in prostate disorder (BPH, PIN and PC) development since might be provoke inhibition of apoptosis and subsequently cell proliferation. At the same time, different transduction pathway such as IL-1/NIK/NF-kB or TNF/NF-kB (NIK or p38) also promotes proliferation. Inhibitions of IAPs, IL-1α and TNFα might be a possible target for PC treatment since IAPs are the proteins that inhibited apoptosis (favour proliferation) and IL-1α and TNFα would affect all the transduction pathway involucrate in the activation of transcription factors related to survival or proliferation (NF-kB, Elk-1 or ATF-2).</p

Beneficial effects of Spirulina Aqueous extract on vasodilator function of arteries from hypertensive rats

9 p.-7 fig.Hypertension is a multifactorial disorder considered one of the major causes of premature death worldwide. This pathology is associated with vascular functional/structural alterations in which nitric oxide (NO) and oxygen reactive species participate. On the other hand, the use of microalgae extracts in the treatment of cardiovascular diseases is increasing. Based on the antioxidant and antihypertensive properties of Spirulina, this study aims to investigate the effect of an aqueous extract of Spirulina on the vasodilator function of the aorta from spontaneously hypertensive rats (SHR), analyzing the functional role of NO. For this, aortic segments from male SHR were divided into two groups, one control and the other exposed to an Spirulina aqueous extract (0.1% w/v, for 3 hours), to analyze (i) the production of NO, superoxide anion, and hydrogen peroxide; (ii) the vasodilator response induced by acetylcholine (ACh), by the NO donor and sodium nitroprusside (SNP), and by the KATP channel opener and pinacidil; and (iii) the expression of the p-Akt, p-eNOS, and HO-1 proteins. The results showed that the aqueous Spirulina extract (i) increased the production of NO, did not significantly modify that of superoxide, while decreased that of hydrogen peroxide; (ii) increased the vasodilatory responses induced by ACh, NPS, and pinacidil; and (iii) increased the expression of p-Akt and HO-1. These results suggest that incubation with the aqueous Spirulina extract improves the vascular function of arteries from SHR by increasing the release/bioavailability/function of NO. Increased KATP channel activation and expression of pAkt and HO-1 appear to be participating in these actions.This study was supported by grants from Comunidad de Madrid (S2013/ABI-2783, “INSPIRΑ1-CM”) and Fondo Europeo de Desarrollo Regional to JLG, CO, and MF; the Spanish Ministerio de Economía, Industria y Competitividad (CTQ2017-86170-R) to CO; and by the Fondo de Investigaciones Sanitarias (PI19/01282) to MF.Peer reviewe