title: Induction of apoptosis in low to moderate-grade human prostate carcinoma by red clover-derived dietary isoflavones.
abstract: Epidemiological evidence suggests a geographical basis for the incidence of prostate cancer and dietary factors, including isoflavone consumption, may be linked to this phenomenon. This paper reports a nonrandomized, nonblinded trial with historically matched controls from archival tissue designed to determine the effects of acute exposure to a dietary supplement of isoflavones in men with clinically significant prostate cancer before radical prostatectomy. Thirty-eight patients were recruited to the study upon diagnosis of prostate cancer. Before surgery, 20 men consumed 160 mg/day of red clover-derived dietary isoflavones, containing a mixture of genistein, daidzein, formononetin, and biochanin A. Serum PSA, testosterone, and biochemical factors were measured, and clinical and pathological parameters were recorded. The incidence of apoptosis in prostate tumor cells from radical prostatectomy specimens was compared between 18 treated and 18 untreated control tissues. There were no significant differences between pre- and posttreatment serum PSA, Gleason score, serum testosterone, or biochemical factors in the treated patients (P > 0.05). Apoptosis in radical prostatectomy specimens from treated patients was significantly higher than in control subjects (P = 0.0018), specifically in regions of low to moderate-grade cancer (Gleason grade 1-3). No adverse events related to the treatment were reported. This report suggests that dietary isoflavones may halt the progression of prostate cancer by inducing apoptosis in low to moderate-grade tumors, potentially contributing to the lower incidence of clinically significant disease in Asian men. The assessment of new prostatic therapies aimed at increasing apoptosis should control for intake of dietary isoflavones.
authors.affiliation: Centre for Urological Research, Monash Institute of Reproduction & Development, Monash University, Victoria 3168, Australia.
authors.forename: Renea A
authors.initials: RA
authors.lastname: Jarred
authors.forename: Mohammad
authors.initials: M
authors.lastname: Keikha
authors.forename: Caroline
authors.initials: C
authors.lastname: Dowling
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: McPherson
authors.forename: Anne M
authors.initials: AM
authors.lastname: Clare
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Husband
authors.forename: John S
authors.initials: JS
authors.lastname: Pedersen
authors.forename: Mark
authors.initials: M
authors.lastname: Frydenberg
authors.forename: Gail P
authors.initials: GP
authors.lastname: Risbridger
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology* / Q000601:surgery; D000368:Aged; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001707:Biopsy, Needle; D019587:Dietary Supplements; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D007529:Isoflavones / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D008517:Phytotherapy / Q000379:methods*; D010936:Plant Extracts / Q000627:therapeutic use; D011300:Preoperative Care; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000032:analysis / Q000187:drug effects*; D011468:Prostatectomy / Q000379:methods; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology* / Q000601:surgery; D012016:Reference Values; D016896:Treatment Outcome; D029921:Trifolium
chemical_list: D007529:Isoflavones; D010936:Plant Extracts; D017430:Prostate-Specific Antigen