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

• Main Authors: Bo-Ram Jin, Se-Yun Cheon, Hyo-Jung Kim, Myoung-Seok Kim, Kwang-Ho Lee, Hyo-Jin An
• Format: Article
• Language: English
• Published: MDPI AG 2020-12-01
• Series: International Journal of Molecular Sciences
• Subjects: benign prostate hyperplasia; cell cycle; <i>Cornus officinalis</i> Sieb. et Zucc.; E2F1; proliferating cell nuclear antigen; proliferation
• Online Access: https://www.mdpi.com/1422-0067/21/24/9567

<i>Cornus officinalis</i>, 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 <i>C. officinalis</i> on prostatic cells. We standardized <i>C. officinalis</i> 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.