The effects of short-term genistein intervention on prostate biomarker expression in patients with localised prostate cancer before radical prostatectomy

Abstract

Nutritionally relevant levels of genistein, the predominant isoflavone in soyabean associated with lower risk of prostate cancer (PCa), may modulate the expression of prostate tissue biomarkers associated with cancer prediction and progression. A phase 2 placebocontrolled, randomised, double-blind clinical trial was conducted in forty-seven Norwegian patients before prostatectomy. Intervention was 30 mg genistein or placebo capsules daily for 3 -6 weeks. Luminal cells from malignant and benign glands were isolated with laser capture microdissection and the mRNA levels of androgen-related biomarkers (androgen receptor, NK3 homeobox 1, kallikrein-related peptide 4 (KLK4)) and cell cycle-related genes ( p21 Waf1/Cip1 , p27 Kip1 , p53) were analysed with real-time semiquantitative PCR. Immunohistochemistry of androgen-, cell cycle-, proliferative-(Ki67 nuclear antigen), apoptotic-(B-cell CLL/lymphoma 2 (BCL-2) and BCL-2-associated X protein) and neuroendocrine differentiation-related biomarkers (neuron-specific enolase and cytoplasmic chromogranin A) was performed using tissue microarrays containing normal, Gleason grade 3 and grade 4 prostate tissues. There were no significant effects by genistein intervention on proliferation-, cell cycle-, apoptosis-or neuroendocrine biomarkers. Genistein intervention, however, significantly reduced the mRNA level of KLK4 in tumour cells (P¼0·033) and there was a nonsignificant reduction in androgen and cell cycle-related biomarkers, except for p27 Kip1 , whose expression in the nuclear compartment was increased. Genistein intervention modulated the expression of several biomarkers which may be related to PCa prediction and progression. The present study supports genistein as a chemopreventive agent in PCa. Further investigation is warranted in larger and longer-duration studies.

Effect of Sulforaphane in Men with Biochemical Recurrence after Radical Prostatectomy

“…In a double-blind placebo-controlled study, green tea catechins (GTC) significantly prevented prostate cancer development in men with highgrade premalignant prostate intraepithelial neoplasia (42). Two randomized, double-blind, placebo-controlled short-term isoflavone intervention trials before radical prostatectomy have shown that genistein failed to change the PSA levels significantly, even though it modulated the expression of several genes involved in prostate cancer (43,44). A 6-month double-blind, placebo-controlled intervention study with highdose soy extracts conducted in 53 men with prostate cancer enrolled in an active surveillance program also failed to show lower PSA levels (45).…”

Influence of Diet and Nutrition on Prostate Cancer

“…A randomized control study of 158 men in eight Japanese centers using a purified isoflavone supplement reported no significant change in the PSA value before and after treatment, and the incidence of PCa showed no significant difference between isoflavone and placebo groups, although for patients aged >65 years, PCa incidence in the isoflavone group was significantly lower (28.0% vs. 57.1%) [116]. Reports of isoflavone supplementation in patients with PCa include multiple randomized controlled trials that suggest that isoflavones show a suppressive effect on PCa progression based on biomarkers, such as serum PSA and testosterone levels [117][118][119][120], although the results have been inconsistent [121]. Such inconsistencies might be related to differences in dosage, duration, and dietary intake by the cohorts in each study.…”

Wnt/beta-catenin pathway: modulating anticancer immune response

“…Phase I and II studies investigating the clinical activity of genistein and other soy isoflavones compounds in cancer treatment and chemoprevention have been published with disappointing results [63–65]. …”