Abstract
BackgroundOur previous study revealed the extract from the bark of an Amazonian tree Pao Pereira can suppress benign prostatic hyperplasia (BPH) in a rat model. Herein, we examined its inhibitory effects on human BPH cells and dissect its molecular mechanism.MethodsWe applied Pao extract to human BPH epithelial BPH-1 and prostate myofibroblast WPMY-1 cells. Cell viability, apoptosis and immunoblotting were performed, followed by gene expression profiling and gene set enrichment analysis (GSEA) to detect the differentially expressed genes and signaling pathway induced by Pao extract. Human ex vivo BPH explant organ culture was also used to examine the effects of Pao extract on human BPH tissues.ResultsPao extract treatment inhibited viability and induced apoptosis in human BPH-1 and WPMY-1 cells. Gene expression profiling and the following validation indicated that the expression levels of pro-apoptotic genes (eg. PCDC4, CHOP and FBXO32) were induced by Pao extract in both two cell lines. GSEA further revealed that Pao extract treatment was negatively associated with the activation of NFκB signaling. Pao extract suppressed the transcriptional activity of NFκB and down-regulated its target genes involved in inflammation (CXCL5, CXCL6 and CXCL12) and extracellular matrix (ECM) remodeling (HAS2, TNC and MMP13) in both cultured cells and human ex vivo BPH explants.ConclusionIn both BPH epithelial and stromal cells, Pao extract induces apoptosis by upregulating the pro-apoptotic genes and inhibiting the inflammation-associated NFκB signaling via reducing phosphorylation of NFκB subunit RelA. Our data suggest that Pao extract may be a promising phytotherapeutic agent for BPH.
Highlights
Our previous study revealed the extract from the bark of an Amazonian tree Pao Pereira can suppress benign prostatic hyperplasia (BPH) in a rat model
Pao extract inhibited proliferation of BPH-1 and WPMY-1 cells To evaluate the effect of Pao extract on the growth of cells derived from the prostate, BPH-1 and WPMY-1 cells were exposed to Pao extract with dosages ranging from 125 to 500 μg/ml, and the cell proliferation were assessed by sulforhodamine B (SRB) assay
Pao extract induced apoptosis in BPH-1 and WPMY-1 cells Flow cytometry analyses were performed to determine whether Pao extract could induce apoptosis in BPH-1 and WPMY-1 cells
Summary
Our previous study revealed the extract from the bark of an Amazonian tree Pao Pereira can suppress benign prostatic hyperplasia (BPH) in a rat model. We examined its inhibitory effects on human BPH cells and dissect its molecular mechanism. Benign prostatic hyperplasia (BPH) is a non-malignant enlargement of the prostate gland that is common in older males. Due to the excessive proliferation of the epithelial and stromal cells in the transition zone and periurethral glands, the enlarged prostate induces lower urinary tract symptoms (LUTS) including urgency and difficulty of urination [2, 3]. The etiology of BPH is multi-factorial, including sex hormones, smooth muscle and inflammation [4]. Medications for BPH/LUTS primarily target sex hormone synthesis and relief of tension in smooth muscle. More effective agents with fewer side effects are needed
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