Kaempferol is a natural compound that inhibits tumor development in androgenic related prostate cancer. However, it is still not clear about its phyto-androgenic activity and whether it suppresses testosterone-induced benign prostatic hyperplasia (BPH) development. In this study, molecular docking, cellular immunofluorescence staining, chromatin immunoprecipitation and dual luciferase reporter assay were performed to investigate the androgenic activity of kaempferol. Dihydrotestosterone-induced gene expression and cell proliferation were further analyzed upon treatment with kaempferol. Testosterone-induced BPH was established in rats then the effect and mechanism of action of kaempferol on BPH development was then assessed. Docking data showed that kaempferol could bind to ASN705 and THR877 residues of androgen receptor which were also the binding sites of dihydrotestosterone. The nuclear translocation of androgen receptor was promoted directly more than 2 percent by kaempferol in androgen-dependent prostate cancer LNCaP cells. In addition, the in vivo interaction of androgen receptor with PSA promoter region and the transcriptional activity of androgen receptor were both significantly enhanced after kaempferol stimulation. However, kaempferol pretreatment suppressed dihydrotestosterone -induced effects including the transcriptional activity of androgen receptor, the expressions of PSA and AR genes and cell proliferation of LNCaP, BPH-1 and WPMY-1 cells. Consistently, kaempferol declined the prostate index almost 30 percent and improved the pathological properties in BPH rats, and the up-regulated T level in serum from BPH rats was highly decreased after kaempferol administration. Kaempferol exhibited its androgenic-like activity and served as a selective androgen receptor modulator that contributes to androgen-related BPH development.
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