Resveratrol induces apoptosis of benign prostatic hyperplasia epithelial cell line (BPH-1) through p38 MAPK-FOXO3a pathway

Abstract

Background Resveratrol is reported to inhibit the growth of prostate, which is characteristic of benign prostatic hyperplasia (BPH) condition. However, the mechanism remains unclear. This study aimed to identify the effects and probable mechanism of resveratrol on BPH. Methods We used the BPH epithelial cell line BPH-1 to investigate the effect of resveratrol. Cells were treated with various concentrations of resveratrol, and its effects on cells viability, apoptosis, ROS accumulation, and cell cycle were assessed. Western blot was used to examine activation of p38 MAPK and protein levels of FOXO3a, Bcl2, Bcl-XL, and caspase3. Cells were also co-treated with the p38 MAPK inhibitor SB203580 or ROS scavenger N-Acetyl-L-cysteine (NAC) to further investigate the mechanism. Results Resveratrol treatment inhibited the growth of BPH-1 and increased apoptosis of cells. In addition, levels of phosphorylated p38 MAPK level was elevated and FOXO3a repression was observed. Concomitantly, ROS was accumulated. All of these resveratrol-mediated effects were suppressed by additional treatment with SB203580 or NAC. Resveratrol was also found to induce cell cycle arrest at S phase. Conclusions Resveratrol can activate p38 MAPK and repress FOXO3a, thereby causing repression of SOD2, catalase, and increase of ROS accumulation, leading to apoptosis in BPH-1 cells.

Peanut Sprout Extracts Cultivated with Fermented Sawdust Medium Inhibits Benign Prostatic Hyperplasia In Vitro and In Vivo

“…It has been demonstrated that RES has many benefits such as anti-cardiovascular effect, anti-tumor effect, anti-oxidant effect, and anti-BPH effect [13,16,26]. Since previous studies have suggested that the peanut sprouts contain high amounts of RES, we investigated the content of RES in 5 types of the Korean peanut varieties (Sindae, Inhua-C, Inhua-W , Inhua-L, and Yesan) germinated for 9 days using sawdust medium fermented for 45 days.…”

“…Kang et al [15] reported that peanut sprouts contain RES, which can be a source of natural antioxidants. Several studies in BPH have suggested that RES inhibits the proliferation of prostatic cells [16].…”

Anti-Inflammatory Action and Mechanisms of Resveratrol

“…In vivo studies reported that maternal dietary resveratrol addition decreased the levels of T cell receptor genes, MAPK signal transduction pathways in weaning piglets, and it alleviated weaning-associated diarrhea and intestinal inflammatory disorders in porcine offspring [116]. Moreover, many studies have shown that this compound could potentially induce apoptosis and in vitro ROS accumulation through p38 MAPK signaling pathways [117][118][119]. Yang et al [120] also reported that resveratrol was able to reduce ROS accumulation, inflammation, and angiogenesis both in vivo and in vitro, then displaying preventive effects for rheumatoid arthritis (RA).…”

Pharmacological Effects and Potential Clinical Usefulness of Polyphenols in Benign Prostatic Hyperplasia

“…Resveratrol has been reported to have anti-proliferative effects not only in cancer cells but also in non-tumor cells, such as pulmonary artery smooth muscle cells [ 120 ]. In an in vitro study, resveratrol inhibited the growth of BPH-1 cells [ 121 ]. In short, flow cytometry indicated that apoptotic cell rates significantly increased in a concentration-dependent manner when resveratrol was administered to BPH-1 cells at various concentrations (20 and 30 μM).…”

“…Furthermore, a Western blot analysis indicated that phosphorylated-p38 mitogen-activated protein kinase (MAPK) level significantly increased after resveratrol treatment, and the expression of Forkhead-box protein O3a (FOXO3a) and anti-apoptotic molecules, such as Bcl2 and Bcl-XL, were downregulated with increased cleaved caspase3 levels. Finally, resveratrol treatment led to enhanced cleaved caspase3 levels [ 121 ]. These results suggested that resveratrol may induce apoptosis via p38 MAPK activation and FOXO3a repression.…”