Secoisolariciresinol diglucoside (SDG), a lignan extracted from flaxseed, has been shown to suppress benign prostatic hyperplasia (BPH). However, little is known about the mechanistic basis for its anti-BPH activity. The present study showed that enterolactone (ENL), the mammalian metabolite of SDG, shared the similar binding site of G1 on a new type membranous estrogen receptor-G Protein-Coupled Estrogen Receptor 1 (GPER) by docking simulations method. ENL and G1 (the specific agonist of GPER) inhibited the proliferation of human prostate stromal cell line WPMY-1 showed by MTT assay and arrested cell cycle at the G0/G1 phase displayed by propidium iodide staining following flow cytometer examination. Silencing GPER by siRNA attenuated the inhibitory effect of ENL on WPMY-1 cells. The therapeutic potential of SDG in the treatment of BPH was confirmed in a testosterone propionate-induced BPH rat model. SDG significantly reduced the enlargement of the rat prostate and the number of papillary projections of prostatic alveolus and thickness of the pseudostratified epithelial and stromal cells when comparing with the model group. Mechanistic studies showed that SDG and ENL increased the expression of GPER both in vitro and in vivo. Furthermore, ENL-induced cell cycle arrest may be mediated by the activation of GPER/ERK pathway and subsequent up-regulation of p53 and p21, down-regulation of cyclin D1. This work, in tandem with previous studies, will enhance our knowledge regarding the mechanism(s) of dietary phytochemicals on BPH prevention and ultimately expand the scope of adopting alternative approaches in BPH treatment.
... Chemicals and reagents Testosterone propionate (TP) was purchased from Shanghai general pharmaceutical co., LTD (Shanghai, China). SDG was from Biopurify Phytochemicals (Chengdu, China). G-1 is from Cayman Chemical (Ann Arbor, MI, USA). We also purchased ...
