title: 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 placebo-controlled, 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 (P = 0·033) and there was a non-significant reduction in androgen and cell cycle-related biomarkers, except for p27Kip1, 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.
authors.affiliation: Department of Urology, Institute of Cancer Research, Oslo University Hospital, The Norwegian Radiumhospital, Montebello, 0310 Oslo, Norway. bato.lazarevic@medisin.uio.no
authors.forename: Bato
authors.initials: B
authors.lastname: Lazarevic
authors.forename: Clara
authors.initials: C
authors.lastname: Hammarström
authors.forename: Jin
authors.initials: J
authors.lastname: Yang
authors.forename: Hakon
authors.initials: H
authors.lastname: Ramberg
authors.forename: Lien M
authors.initials: LM
authors.lastname: Diep
authors.forename: Steinar J
authors.initials: SJ
authors.lastname: Karlsen
authors.forename: Omer
authors.initials: O
authors.lastname: Kucuk
authors.forename: Fahri
authors.initials: F
authors.lastname: Saatcioglu
authors.forename: Kristin A
authors.initials: KA
authors.lastname: Taskèn
authors.forename: Aud
authors.initials: A
authors.lastname: Svindland
mesh_terms: D000728:Androgens / Q000235:genetics; D016588:Anticarcinogenic Agents; D017209:Apoptosis / Q000235:genetics; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics; D049109:Cell Proliferation; D004311:Double-Blind Method; D015870:Gene Expression / Q000187:drug effects; D019833:Genistein / Q000008:administration & dosage*; D006801:Humans; D007610:Kallikreins / Q000235:genetics; D008297:Male; D009664:Norway; D010919:Placebos; D011467:Prostate / Q000473:pathology; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000737:chemistry* / Q000473:pathology / Q000601:surgery*; D012333:RNA, Messenger / Q000032:analysis; D011944:Receptors, Androgen / Q000235:genetics; D046888:Tissue Array Analysis
chemical_list: D000728:Androgens; D016588:Anticarcinogenic Agents; D014408:Biomarkers, Tumor; D010919:Placebos; D012333:RNA, Messenger; D011944:Receptors, Androgen; D019833:Genistein; D007610:Kallikreins; C120801:kallikrein 4