lignans and Prostatic-Hyperplasia

Both benign hyperplasia (BPH) and cancer of the prostate are manifest in men beyond the age of 50. Approximately 50% of men greater than 50 years of age will suffer from the symptoms associated with BPH, especially from bladder outlet obstruction. With the ever-increasing proportion of the population over 65 years of age worldwide, BPH is becoming an important medical problem as the world moves into the next millennium. Cancer of the prostate is the second most commonly diagnosed cancer after skin cancer in the male population of the United States, and the second most common cause of death from cancer after that of the lung. Overall, around the world the incidence of carcinoma of the prostate is increasing annually by 2-3%. Both race and geographical location have a profound influence of the prevalence of prostate cancer worldwide. Black men in the USA have the highest incidence, while the incidence is much lower in Asian men from China, Japan and Thailand. Although the prostate gland is androgen-dependent, it is now recognized that the biological actions of endocrine-related factors, such as androgens, oestrogens, glucocorticoids and certain dietary and environmental factors, are mediated within the gland by various growth regulatory factors. The growth regulatory factors such as epidermal growth factor (EGF), keratinocyte growth factors (KGF), fibroblast growth factors (FGFs) and insulin-like growth factors II and I are mitogenic and directly stimulate cell proliferation under the modulating influence of steroid hormones. Steroids are therefore essential but not directly responsible for cell proliferation. Certain plant compounds such as isoflavonoids, flavonoids and lignans have been proposed as cancer protective compounds in populations with low incidences of prostate diseases. In particular, soya contains the isoflavone genistein, a compound with many properties which could influence both endocrine and growth factor signalling pathways.

Topics: Estrogens, Non-Steroidal; Humans; Isoflavones; Lignans; Male; Phytoestrogens; Plant Preparations; Prostatic Diseases; Prostatic Hyperplasia; Prostatic Neoplasms

A flaxseed lignan extract containing 33% secoisolariciresinol diglucoside (SDG) was evaluated for its ability to alleviate lower urinary tract symptoms (LUTS) in 87 subjects with benign prostatic hyperplasia (BPH). A randomized, double-blind, placebo-controlled clinical trial with repeated measurements was conducted over a 4-month period using treatment dosages of 0 (placebo), 300, or 600 mg/day SDG. After 4 months of treatment, 78 of the 87 subjects completed the study. For the 0, 300, and 600 mg/day SDG groups, respectively, the International Prostate Symptom Score (IPSS) decreased -3.67 +/- 1.56, -7.33 +/- 1.18, and -6.88 +/- 1.43 (mean +/- SE, P = .100, < .001, and < .001 compared to baseline), the Quality of Life score (QOL score) improved by -0.71 +/- 0.23, -1.48 +/- 0.24, and -1.75 +/- 0.25 (mean +/- SE, P = .163 and .012 compared to placebo and P = .103, < .001, and < .001 compared to baseline), and the number of subjects whose LUTS grade changed from "moderate/severe" to "mild" increased by three, six, and 10 (P = .188, .032, and .012 compared to baseline). Maximum urinary flows insignificantly increased 0.43 +/- 1.57, 1.86 +/- 1.08, and 2.7 +/- 1.93 mL/second (mean +/- SE, no statistical significance reached), and postvoiding urine volume decreased insignificantly by -29.4 +/- 20.46, -19.2 +/- 16.91, and -55.62 +/- 36.45 mL (mean +/- SE, no statistical significance reached). Plasma concentrations of secoisolariciresinol (SECO), enterodiol (ED), and enterolactone (EL) were significantly raised after the supplementation. The observed decreases in IPSS and QOL score were correlated with the concentrations of plasma total lignans, SECO, ED, and EL. In conclusion, dietary flaxseed lignan extract appreciably improves LUTS in BPH subjects, and the therapeutic efficacy appeared comparable to that of commonly used intervention agents of alpha1A-adrenoceptor blockers and 5alpha-reductase inhibitors.

Topics: Aged; Aged, 80 and over; Butylene Glycols; Diet; Double-Blind Method; Flax; Glucosides; Humans; Lignans; Male; Middle Aged; Phytotherapy; Placebos; Plant Extracts; Prostatic Hyperplasia; Quality of Life; Urinary Tract; Urination; Urine

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 of membranous estrogen receptor, G-protein-coupled estrogen eceptor 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 as shown by MTT assay and arrested cell cycle at the G0/G1 phase, which was displayed by propidium iodide staining following flow cytometer examination. Silencing GPER by short interfering RNA 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 upregulation of p53 and p21 and downregulation 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.

Topics: 4-Butyrolactone; Animals; Antineoplastic Agents, Phytogenic; Binding Sites; Butylene Glycols; Cell Line, Tumor; Cell Proliferation; Dietary Supplements; Flax; Gene Expression Regulation, Neoplastic; Glucosides; Glycosides; Humans; Lignans; Male; Models, Molecular; Molecular Docking Simulation; Neoplasm Proteins; Prostate; Prostatic Hyperplasia; Random Allocation; Rats; Rats, Wistar; Receptors, Estrogen; Receptors, G-Protein-Coupled; RNA Interference; Seeds

Consumption of diet rich in lignans may decrease the risk of some chronic hormonal conditions such as benign prostatic hyperplasia (BPH). This study investigated whether a lignan-rich extract from flaxseed hulls, LinumLife EXTRA (LLE), could prevent BPH using the testosterone propionate (TP)-induced BPH rat model. Male Wistar-Unilever rats were randomly divided into four groups of 12 rats each: a negative control group fed with control diet and receiving daily subcutaneous injections of corn oil without TP, and three groups fed with control diet (positive control), diet containing 0.5% LLE (LLE 0.5) or 1.0% LLE (LLE 1.0) and receiving daily subcutaneous injections of TP in corn oil. Treatments with diets started 2 weeks before the induction of BPH and were carried out for 5 consecutive weeks. The influence of TP and LLE on body weight (BW), food and water consumptions, and enterolactone (ENL) levels in serum and urine of rats was examined at the end of the 5-week treatment period. TP significantly diminished the mean body weight gain (MBWG) of positive control rats and their food and water consumptions while LLE reduced significantly this MBWG reduction in a dose-dependent manner. The lignan-rich extract significantly inhibited TP-induced prostate size ratio (prostate weight/rat BW) increase in comparison with positive controls (P<.001). This effect was dose dependent. Higher serum and urine levels of ENL correlated well with the dose of extract provided to rats. It was concluded that the lignan-rich flaxseed hull extract prevented the TP-induced BPH indicating it might be beneficial in the prevention of BPH.

Topics: 4-Butyrolactone; Animals; Disease Models, Animal; Dose-Response Relationship, Drug; Drinking; Energy Intake; Flax; Hyperplasia; Lignans; Male; Phytotherapy; Plant Extracts; Prostate; Prostatic Hyperplasia; Rats, Wistar; Seeds; Testosterone Propionate; Weight Gain

To compare phytoestrogen tissue levels in men with small-volume benign prostatic hyperplasia (BPH), large-volume BPH, and prostate cancer (PCa).. Prostatic tissue samples of men consuming a Western diet who underwent surgery for BPH (n = 63) or PCa (n = 31) were collected and frozen at -40 degrees C. In the tissue samples, the enterolactone and genistein levels were determined in duplicate by monoclonal antibody-based immunoassays. We subsequently compared the tissue levels in patients with BPH and PCa and studied the impact of enterolactone and genistein on prostate volume.. The enterolactone tissue levels were comparable in patients with BPH and PCa and revealed no correlation to prostate volume. The genistein tissue levels tended to be lower in patients with PCa (median 8.4 ng/g dry weight) compared with the entire BPH group (11.0 ng/g dry weight; P = 0.072). In addition, the genistein tissue levels were significantly greater in men with small-volume BPH (median 20.9 ng/g dry weight) compared with those with large-volume BPH (8.8 ng/g dry weight; P = 0.023).. Our data suggest an involvement of genistein in the pathogenesis of BPH and, possibly, of PCa. The impact of enterolactone is currently unknown.

Topics: 4-Butyrolactone; Adenocarcinoma; Aged; Aged, 80 and over; Diet; Genistein; Humans; Lignans; Male; Middle Aged; Organ Size; Phytoestrogens; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms

Isoflavones and lignans are phytoestrogens that have recently gained interest as dietary factors related to prostatic diseases. However, no data on the concentrations in prostate tissue in humans is available. Therefore, the concentrations of isoflavones and lignans in plasma and prostatic tissues according to the prostate volume were compared to determine their possible effect on the benign prostatic growth.. Fasting plasma and prostatic tissue specimens were acquired from 25 men over 50 years of age with similar normal dietary habits and no previous history of drug intake that could affect the isoflavones and lignans levels. The tissue was acquired either during a transurethral resection of the prostate in 15 patients with benign prostatic hyperplasia (BPH) with prostate volume over 40 ml or during a radical cystoprostatectomy in 10 patients with bladder cancer with a prostate volume < 25 ml, who were used as the controls. Quantitative analysis of the isoflavones, specifically equol, daidzein and genistein and lignans, particularly enterodiol and enterolactone, was performed by gas chromatography-mass spectrometry.. The mean prostatic concentrations of enterodiol, enterolactone, equol and daidzein in the BPH and the control groups were similar. However, the mean prostatic concentration of genistein was significantly lower in the BPH group than in the control group (65.43 +/- 17.05 vs 86.96 +/- 37.75 ng/ ml, respectively, p=0.032). The plasma concentration of isoflavones and lignans in the two groups were comparable.. Isoflavones, but not lignans, have some influence the benign prostatic growth, and the prostatic concentration of genistein possibly has the closest association among them. More studies to further clarify the roles and mechanisms of isoflavone action on BPH including pharmacokinetic studies are recommended.

Topics: Blood; Humans; Isoflavones; Lignans; Male; Middle Aged; Osmolar Concentration; Prostate; Prostatic Hyperplasia; Reference Values

Isoflavonoids and lignans, constituents of many plant foods, have been proposed as protective agents in those populations with a low incidence of hormone-dependent cancers. They may act by their inhibition of the metabolism of growth-promoting steroid hormones. This report describes the inhibition of 5 alpha-reductase and 17 beta-hydroxysteroid dehydrogenase by six isoflavonoids and two lignans in human genital skin fibroblast monolayers and homogenates, and in benign prostatic hyperplasia tissue homogenates. In genital skin fibroblasts, genistein, biochanin A and equol were the most potent inhibitors of 5 alpha-reductase activity, each resulting in greater than 80% inhibition at a concentration of 100 microM. The IC50 values for genistein and a seven-compound mixture were approximately 35 microM and 20 microM (2.9 microM of each compound) respectively. Of the lignans, enterolactone was the most potent inhibitor. Inhibition by biochanin A was shown to be reversible. When genital skin fibroblast homogenates were used, biochanin A was found to inhibit 5 alpha-reductase isozymes 1 and 2 to differing extents (30% and 75% respectively). Genistein was shown to inhibit 5 alpha-reductase 2 in a non-competitive nature (Vmax and Km values without and with inhibitor were 30 and 20 pmol/mg protein per h and 177 and 170 nM respectively). All of the compounds tested inhibited 17 beta-hydroxysteroid dehydrogenase activity in genital skin fibroblast monolayers. When prostate tissue homogenates were used, the compounds tested were better inhibitors of 5 alpha-reductase 1 than 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 17-Hydroxysteroid Dehydrogenases; 3-Oxo-5-alpha-Steroid 4-Dehydrogenase; Chromans; Depression, Chemical; Equol; Fibroblasts; Genistein; Humans; Isoflavones; Lignans; Male; Prostate; Prostatic Hyperplasia; Skin; Testis