Department of Drug and Health Sciences, University of Catania, 95125 Catania, Italy.
CERNUT-Research Centre for Nutraceuticals and Health Products, University of Catania, 95125 Catania, Italy.
Int J Mol Sci. 2023 Jun 27;24(13):10719. doi: 10.3390/ijms241310719.
Benign prostatic hypertrophy (BPH) is a noncancerous enlargement of the prostate gland that develops from hyper-proliferation of the stromal and epithelium region. Activation of pathways involving inflammation and oxidative stress can contribute to cell proliferation in BPH and tumorigenesis. Agricultural-waste-derived extracts have drawn the attention of researchers as they represent a valid and sustainable way to exploit waste production. Indeed, such extracts are rich in bioactive compounds and can provide health-promoting effects. In particular, extracts obtained from pomegranate wastes and by-products have been shown to exert antioxidant and anti-inflammatory effects. This study focused on the evaluation of the anti-angiogenic effects and chemopreventive action of a pomegranate extract (PWE) in cellular models of BPH. In our experimental conditions, we observed that PWE was able to significantly ( < 0.001) reduce the proliferation and migration rates (up to 60%), together with the clonogenic capacity of BPH-1 cells concomitantly with the reduction in inflammatory cytokines (e.g., IL-6, PGE2) and pro-angiogenic factor (VEGF-ADMA) release. Additionally, we demonstrated the ability of PWE in reducing angiogenesis in an in vitro model of BPH consisting in transferring BPH-1-cell-conditioned media to human endothelial H5V cells. Indeed, PWE was able to reduce tube formation in H5V cells through VEGF level reduction even at low concentrations. Overall, we confirmed that inhibition of angiogenesis may be an alternative therapeutic option to prevent neovascularization in prostate tissue with BPH and its transformation into malignant prostate cancer.
良性前列腺增生(BPH)是前列腺腺体的非癌性增大,源于基质和上皮区域的过度增殖。涉及炎症和氧化应激的途径的激活可能导致 BPH 中的细胞增殖和肿瘤发生。农业废物衍生的提取物引起了研究人员的关注,因为它们代表了一种有效和可持续的利用废物生产的方式。事实上,这些提取物富含生物活性化合物,并能提供促进健康的作用。特别是,从石榴废物和副产品中获得的提取物已被证明具有抗氧化和抗炎作用。本研究集中于评估石榴提取物(PWE)在 BPH 细胞模型中的抗血管生成作用和化学预防作用。在我们的实验条件下,我们观察到 PWE 能够显著(<0.001)降低 BPH-1 细胞的增殖和迁移率(高达 60%),同时降低炎症细胞因子(如 IL-6、PGE2)和促血管生成因子(VEGF-ADMA)的释放。此外,我们还证明了 PWE 在降低 BPH-1 细胞条件培养基转染到人内皮 H5V 细胞的体外 BPH 模型中的血管生成能力。事实上,PWE 能够通过降低 VEGF 水平来减少 H5V 细胞中的管形成,即使在低浓度下也是如此。总的来说,我们证实抑制血管生成可能是预防 BPH 前列腺组织新生血管形成及其向恶性前列腺癌转化的另一种治疗选择。