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Lignans Research: Prostate Health

In a recent study Bylund A et al (2005) investigated the effect of a plant lignan 7-hydroxymatairesinol (HMR) on LNCaP human prostate cancer xenografts in athymic mice. Result showed that an HMR diet significantly inhibited the growth of LNCaP tumors. Mice treated with HMR had smaller tumor volume, lower tumor take rate, increased proportion of non-growing tumors, and higher tumor cell apoptotic index compared with controls. Furthermore, the cell proliferation index was reduced in mice receiving the 0.30% HMR diet compared with mice receiving the control diet1.  

In a 2006 Swedish study Hedelin et al, investigated evidence that phytoestrogens may protect against prostate cancer and the associations between serum enterolactone concentration or dietary phytoestrogen intake and risk of prostate cancer. Questionnaire-data was collected on 1,499 prostate cancer cases and 1,130 control cases with serum enterolactone levels measured in a sub-group of 209 cases and 214 controls. Unconditional logistic regression was performed to estimate multivariate odds ratios (ORs) and 95% confidence intervals (CIs) for associations with risk of prostate cancer. Results revealed that a high intake of food items rich in phytoestrogens was associated with a decreased risk of prostate cancer. Although no association was seen between dietary intake of total or individual lignans or isoflavonoids and risk of prostate cancer intermediate serum levels of enterolactone were associated with a decreased risk of prostate cancer2.

In a pilot study to explore effects of low-fat, flaxseed-supplemented diet on proliferation of benign prostatic epithelium and prostate-specific antigen Demark-Wahnefried et al (Journal of Urology. 2004) investigated the hypothesis that dietary factors may influence the prostate and have an impact on prostatic growth and disease. In the study fifteen men who were scheduled to undergo repeat prostate biopsy were instructed to follow a low-fat (less than 20% kcal), flaxseed-supplemented (30 g/day) diet and were provided with a supply of flaxseed to last throughout the 6-month intervention period. Results showed a statistically significant decreases in PSA and cholesterol. Of the 13 men who underwent repeat biopsy, the proliferation rates in the benign epithelium decreased significantly. The study concluded that flaxseed-supplemented, fat-restricted diet may affect the biology of the prostate and associated biomarkers3.

Research into the effect of mammalian lignans on the growth of prostate cancer cell lines at the Duke University Medical Center, Durham, USA investigated the effects of enterodiol (ED) and enterolactone (EL) on three human prostate cancer cell lines (PC-3, DU-145 and LNCaP). showed at 10-100 microM, EL significantly inhibited the growth of all cell lines, whereas ED only inhibited PC-3 and LNCaP cells. The study research concluded that both ED and EL suppress the growth of prostate cancer cells, and may do so via hormonally-dependent and independent mechanisms4.

In an animal study in Japan (2004), Hydroxymatairesinol obtained from the heartwood of spruce (Picea abies), was demonstrated to exert chemo-preventive effects on the development of mammary tumours in rats. To examine the influence of HMR on uterine carcinogenesis, adult Donryu rats were initiated with a single intrauterine treatment of N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) at 11 weeks of age and fed thereafter 0, 200, or 600 ppm HMR mixed in the soy-containing diet until 15 months of age. Incidences of uterine adenocarcinoma in both 200 and 600 ppm HMR-dosed groups were significantly reduced to 11% and 15%, respectively, less than 50% of 0 ppm, at the end of the experiment (P < 0.05). A delay in the start of persistent estrus by HMR was observed at 8 months of age compared with controls given carcinogen alone. From urinalysis, HMR was metabolized mainly to enterolactone and hydroxyl-enterolactone. The study concluded that the findings suggest that HMR or its metabolites may exert chemo-preventive effects in the rat ENNG-uterine carcinogenesis model5.

In a randomised controlled short-term intervention pilot study on rye bran bread in prostate cancer the short-term effects of rye bran bread intake in prostate cancer were investigated. Ten men with conservatively treated prostate cancer were randomised to a daily supplement of 295 g of rye bran bread and eight men to 275 g of wheat bread (control) with similar fibre content for three weeks. Blood samples, ultrasound-guided core biopsies of the prostate, and urine samples were taken. In the rye group, there was a significant increase in plasma enterolactone, and the apoptotic index increased significantly from 2.1% (SD 1.3) to 5.9% (SD 1.8), P<0.005 as measured by a TUNEL index in four cases in the rye group and seven cases in the control group. Besides a significant decrease in weight in both groups, only small changes were observed in plasma concentrations of prostate specific antigen (PSA), circulating sex hormones, excreted oestrogens, insulin-like growth factor (IGF)-I, and in the endothelial fibrinolytical system. High intake of rye bran bread is suggested to increase apoptosis in prostate tumours6.

 

 
 

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1. Exp Biol Med (Maywood). 2005 Mar;230(3):217-23. Anticancer effects of a plant lignan 7-hydroxymatairesinol on a prostate cancer model in vivo. Bylund A, Saarinen N, Zhang JX, Bergh A, Widmark A, Johansson A, Lundin E, Adlercreutz H, Hallmans G, Stattin P, Makela S. University of Turku, Functional Foods Forum, FI-20014 Turku, Finland.

2. Cancer Causes Control. 2006 Mar;17(2):169-80. Dietary phytoestrogen, serum enterolactone and risk of prostate cancer: the cancer prostate sweden study (sweden).Hedelin M, Klint A, Chang ET, Bellocco R, Johansson JE, Andersson SO, Heinonen SM, Adlercreutz H, Adami HO, Gronberg H, Balter KA.Department
of Medical Epidemiology and Biostatistics, Karolinska Institutet, Box 281, SE-171 77, Stockholm, Sweden, maria.hedelin@ki.se.


3. Urology. 2004 May;63(5):900-4. Pilot study to explore effects of low-fat, flaxseed-supplemented diet on proliferation of benign prostatic epithelium and prostate-specific antigen. Demark-Wahnefried W, Robertson CN, Walther PJ, Polascik TJ, Paulson DF, Vollmer RT. Division of Urologic Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.

4. Anticancer Res. 2001 Nov-Dec;21(6A):3995-9. Effect of mammalian lignans on the growth of prostate cancer cell lines. Lin X, Switzer BR, Demark-Wahnefried W. Division of Urologic Surgery, Duke University Medical Center, Durham, NC 27710, USA. lin00026@mc.duke.edu.


5. Exp Biol Med (Maywood). 2004 May;229(5):417-24. Chemopreventive effects of hydroxymatairesinol on uterine carcinogenesis in Donryu rats. Katsuda S, Yoshida M, Saarinen N, Smeds A, Nakae D, Santti R, Maekawa A. Department of Biological Safety Research, Japan Food Research Laboratories, Tama-shi, Tokyo 206-0025, Japan. katudas@jfrl.or.jp

6. Eur J Cancer Prev. 2003 Oct;12(5):407-15. Randomised controlled short-term intervention pilot study on rye bran bread in prostate cancer. Bylund A, Lundin E, Zhang JX, Nordin A, Kaaks R, Stenman UH, Aman P, Adlercreutz H, Nilsson TK, Hallmans G, Bergh A, Stattin P. Department of Community Medicine and Rehabilitation Geriatric Medicine, University of Umea, Sweden.