Induction of Apoptosis in Low to Moderate-Grade Human Prostate Carcinoma by Red Clover-derived Dietary Isoflavones

Induction of Apoptosis in Low to Moderate-Grade Human Prostate Carcinoma by Red Clover-derived Dietary Isoflavones1

Centre for Urological Research, Monash Institute of Reproduction & Development, Monash University, Victoria 3168, Australia [R. A. J., M. K., C. D., S. J. M., J. S. P., M. F., G. P. R.]; Department of Surgery, Monash University, Victoria 3168, Australia [M. F.]; Department of Urology, Monash Medical Centre, Victoria 3168, Australia [A. M. C., M. F.]; and Faculty of Veterinary Science, University of Sydney, New South Wales 2006, Australia [A. J. H.]

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.

Footnotes

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
↵1 Supported, in part, by a Program Grant 97/3218 from National Health and Medical Research Council (NH&MRC) of Australia and Novogen Ltd. (North Ryde, NSW, Australia).
↵2 To whom requests for reprints should be addressed, at Monash Institute of Reproduction and Development, Monash University, 27-31 Wright Street, Clayton, Australia, 3168. Phone: (613) 9594-7117; Fax: (613) 9594-7115; E-mail: gail.risbridger{at}med.monash.edu.au
↵3 The abbreviations used are: BPH, benign prostatic hyperplasia; ER, estrogen receptor; AR, androgen receptor; PSA, prostate specific antigen; TNM, Tumor-Node-Metastasis; AE, adverse event.
- Accepted October 4, 1902.
- Received March 11, 1902.
- Revision received September 24, 1902.