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.
Highlights
benign prostatic hyperplasia (BPH) is defined as the enlargement of the prostate gland and is a common disease in aging men
We explored the effects of C. officinalis 30% ethanol extract (COFE) on the development and progression of BPH and the involvement in Proliferating cell nuclear antigen (PCNA)/E2F1-dependent cell cycle pathway
We have demonstrated the inhibitory effect on the BPH progression via E2F1/pRB/PCNA-dependent cell cycle signaling pathway regulation [25]
Summary
BPH is defined as the enlargement of the prostate gland and is a common disease in aging men. The etiology of BPH is not fully elucidated, evidence suggest that male sex hormones and aging are important factors for the development of BPH [3]. Androgenic hormones, testosterone, and dihydrotestosterone (DHT), are important determinants of the pathogenesis of BPH. To improve BPH-associated lower urinary tract symptoms, androgen ablation therapy, such as the use of finasteride and other 5α-reductase inhibitors, forms the basis of medication [4]. These treatments are not completely successful owing to the risk of adverse reactions, such as fatigue, weakness, insomnia, sexual dysfunction, and prostate cancer. A clear understanding of its molecular mechanisms is still lacking, suggesting that substitutional agents that could exert more effective functions and reduce side effects in clinical use are required
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