Inhibition of α1-Adrenergic, Non-Adrenergic and Neurogenic Human Prostate Smooth Muscle Contraction and of Stromal Cell Growth by the Isoflavones Genistein and Daidzein

Abstract

Isoflavone-rich legumes, including soy, are used for food production, as dietary supplements and in traditional medicine. Soy consumption correlates negatively with benign prostatic hyperplasia (BPH) and voiding symptoms. However, isoflavone effects on the prostate are hardly known. Here, we examined the effects on human prostate smooth muscle contractions and stromal cell growth, which are driving factors of voiding symptoms in BPH. Smooth muscle contractions were induced in prostate tissues from radical prostatectomy. Growth-related functions were studied in cultured stromal cells (WPMY-1). Neurogenic, α1-adrenergic and non-adrenergic contractions were strongly inhibited with 50 µM and by around 50% with 10 µM genistein. Daidzein inhibited neurogenic contractions using 10 and 100 µM. Agonist-induced contractions were inhibited by 100 µM but not 10 µM daidzein. A combination of 6 µM genistein with 5 µM daidzein still inhibited neurogenic and agonist-induced contractions. Proliferation of WPMY-1 cells was inhibited by genistein (>50%) and daidzein (<50%). Genistein induced apoptosis and cell death (by seven-fold relative to controls), while daidzein induced cell death (6.4-fold) without apoptosis. Viability was reduced by genistein (maximum: 87%) and daidzein (62%). In conclusion, soy isoflavones exert sustained effects on prostate smooth muscle contractions and stromal cell growth, which may explain the inverse relationships between soy-rich nutrition, BPH and voiding symptoms.

Selective inhibition of neurogenic, but not agonist‐induced contractions by phospholipase A2 inhibitors points to presynaptic phospholipase A2 functions in contractile neurotransmission to human prostate smooth muscle

“…Prostate strips (6 × 3 × 3 mm) were mounted in organ baths (Danish Myotechnology) with four chambers, stretched to 4.9 mN, equilibrated, and contracted by 80 mM KCl as previously described 10 . Following washout of KCl, inhibitors or solvent (dimethylsulfoxide, DMSO, or ethanol) for controls were added.…”

“…Cumulative concentration response curves for α 1 ‐adrenergic agonists or frequency response curves for electric field stimulation (EFS) were constructed 30 min after addition of inhibitors or solvent. EFS induces neurogenic contractions, and was applied as previously described 10 …”

“…Prostate strips (6 × 3 × 3 mm) were mounted in organ baths (Danish Myotechnology) with four chambers, stretched to 4.9 mN, equilibrated, and contracted by 80 mM KCl as previously described. 10 Following washout of KCl, inhibitors or solvent (dimethylsulfoxide, DMSO, or ethanol) for controls were added. Cumulative concentration response curves for α 1 -adrenergic agonists or frequency response curves for electric field stimulation (EFS) were constructed 30 min after addition of inhibitors or solvent.…”

“…EFS induces neurogenic contractions, and was applied as previously described. 10 Each independent experiment was performed using tissue from the same prostate, which was examined with inhibitor and as control group. Only one concentration response or frequence response curve was recorded with each sample.…”

Inhibition of growth and contraction in human prostate stromal cells by silencing of NUAK1 and -2, and by the presumed NUAK inhibitors HTH01-015 and WZ4003

“…Prostate strips (6 × 3 × 3 mm) were mounted in organ baths (Danish Myotechnology, Aahus, Denmark) with four chambers, stretched to 4.9 mN, equilibrated, and contracted by 80 mM KCl as previously described (Huang et al, 2022). Following washout of KCl, HTH01-015, WZ4003 or equivalent amounts of solvent for controls were added.…”