Anti-Proliferative Effects of Standardized Cornus officinalis on Benign Prostatic Epithelial Cells via the PCNA/E2F1-Dependent Cell Cycle Pathway

Abstract

Cornus officinalis, widely used in traditional Chinese medicine, exhibits pharmacological effects against erectile dysfunction and pollakisuria, which are pathological symptoms of benign prostatic hyperplasia (BPH). Although traditional usage and a study on BPH have been reported, to our knowledge, no study has investigated the exact molecular mechanism(s) underlying the anti-proliferative effects of standardized C. officinalis on prostatic cells. We standardized C. officinalis 30% ethanol extract (COFE) and demonstrated the therapeutic effects of COFE on human BPH epithelial cells and testosterone-induced BPH in rats. In vitro studies using BPH-1 cells demonstrated an upregulation of BPH-related and E2F Transcription Factor 1(E2F1)-dependent cell cycle markers, whereas treatment with COFE clearly inhibited the proliferation of BPH epithelial cells and reduced the overexpression of G1 and S checkpoint genes. Additionally, COFE administration alleviated the androgen-dependent prostatic enlargement in a testosterone-induced BPH animal model. COFE exerted these anti-BPH effects by the inhibition of anti-apoptotic markers, suppression of PCNA expression, and regulation of E2F1/pRB-dependent cell cycle markers in rats with BPH. These results suggest that COFE exerts anti-proliferative effect by regulating PCNA/E2F1-dependent cell cycle signaling pathway both in vivo and in vitro. These findings reveal the therapeutic potential of COFE, which could be used as a substitute for BPH treatment.

Voratins A–C: Pyridinium Alkaloids from the Marine Dinoflagellate Effrenium voratum with Inhibitory Effects on Biomarkers for Benign Prostatic Hyperplasia

“…A significant increase in PCNA gene expression has been observed in the prostatic tissues of BPH rats. Moreover, upregulation of PSA secretion has been observed in BPH patients . In LNCap cells, the expression of PSA induced by TP is inhibited by 2 and 3 .…”

Mixture of Corni Fructus and Schisandrae Fructus improves testosterone-induced benign prostatic hyperplasia through regulating 5α-reductase 2 and androgen receptor

“…This means that homeostasis of prostate cell growth and apoptosis are important for the progression of BPH [ 51 ]. Considering the antiproliferative properties of CF and SF in cultured human BPH epithelial and prostate smooth muscle cells [ 52 53 ], respectively, MIX might affect growth factors and apoptosis-related regulatory proteins in prostate cells. These assumptions led us to investigate the effect of MIX on the expression of growth factors and apoptosis factors in BPH rats.…”