期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 21, 期 24, 页码 -出版社
MDPI
DOI: 10.3390/ijms21249567
关键词
benign prostate hyperplasia; cell cycle; Cornus officinalis Sieb; et Zucc; proliferating cell nuclear antigen; proliferation
资金
- National Research Foundation of Korea (NRF) - Ministry of Science, ICT and Future Planning [NRF2019R1A2C4070234]
- Korea Health Industry Development Institute (KHIDI) - Ministry of Health & Welfare, Republic of Korea [HF20C0080]
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.
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