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Phytoestrogens and prostate cancer: experimental, clinical, and epidemiological studies
Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences.
2007 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Dietary factors may affect development and progression of prostate cancer. Experimental and epidemiological studies have suggested an effect of phytoestrogens on prostate cancer. Lignans are the predominant phytoestrogen in a Western diet.

The effects of a diet rich in phytoestrogens and in particular lignans, as compared to a control diet, were assessed in several prostate cancer models.

In paper I, 70 athymic nude mice with transplanted subcutaneous LNCaP tumours, an androgen sensitive human prostate cancer cell line, were fed one out of six phytoestrogen rich diets or a control diet after tumour injection. The rye diet, with high lignan content, decreased tumour take and growth, decreased secretion of prostate specific antigen and increased apoptosis. Addition of fat to the rye diet decreased the beneficial effects.

In paper II, transgenic mice designed to develop prostate cancer (TRAMP) were fed rye bran or a control diet from the age of four weeks. Rye bran decreased prostate epithelial cell volume by 20%, and increased cell apoptosis by 31% as compared to the control diet.

In paper III, we examined the effects of 7-hydroxymatairesinol (HMR), a purified lignan, in nude mice with subcutaneous LNCaP tumours in two different concentrations as compared to a control diet. Mice on the HMR diets had a reduced tumour take rate, lower total tumour volume, increased proportion of non-growing tumours, and increased apoptosis as compared to the control diet.

Paper IV was a three week intervention study exploring the effects of rye bran bread vs. a control diet in men with prostate cancer. The men in the rye group had increased levels of plasma enterolactone and in biopsies from the prostate after the intervention an increase in apoptosis was observed in comparison with biopsies obtained before the intervention.

In paper V, we examined the association between plasma levels of enterolactone, and risk of prostate cancer in a nested case control study. In the Northern Sweden Health and Disease Cohort, enterolactone concentrations were measured in plasma obtained at a mean time of 5 years before diagnosis from 265 cases of prostate cancer, and from 525 matched controls. We found no significant association between plasma enterolactone and risk of prostate cancer. Men with very low enterolactone levels (bottom decile) however, had significantly higher risk of prostate cancer.

Phytoestrogen rich diet including soy, rye bran, substances purified from rye, and a purified lignan (HMR) all inhibited prostate tumour growth. However, it cannot be concluded that the effects observed were due solely to lignans as other components in rye grain such as tannins, phytic acid, ferulic acid, vitamins and minerals may have contributed to the beneficial effects. Thus, additional studies are needed to further elucidate the effects of phytoestrogens on prostate cancer development and progression.

Place, publisher, year, edition, pages
Umeå: Kirurgisk och perioperativ vetenskap , 2007. , 49 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1127
Keyword [en]
prostatic neoplasm, phytoestrogens, lignans, enterolactone, rye, 7-hydroxymataireorcinol, nude mice, TRAMP mice, nested case control study, LNCaP
Research subject
Oncology
Identifiers
URN: urn:nbn:se:umu:diva-1402ISBN: 978-91-7264-418-2 (print)OAI: oai:DiVA.org:umu-1402DiVA: diva2:140916
Public defence
2007-11-09, Sal 1, by 10(Sut), NUS, Umeå, 09:00 (English)
Opponent
Supervisors
Available from: 2007-10-25 Created: 2007-10-25 Last updated: 2009-05-15Bibliographically approved
List of papers
1. Rye bran and soy protein delay growth and increase apoptosis of human LNCaP prostate adenocarcinoma in nude mice
Open this publication in new window or tab >>Rye bran and soy protein delay growth and increase apoptosis of human LNCaP prostate adenocarcinoma in nude mice
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2000 (English)In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 42, no 4, 304-314 p.Article in journal (Refereed) Published
Identifiers
urn:nbn:se:umu:diva-2676 (URN)10679760 (PubMedID)
Available from: 2007-10-25 Created: 2007-10-25 Last updated: 2017-12-14Bibliographically approved
2. Epithelial cell apoptosis and decreases epithelial cell volume in TRAMP (transgenic adenocarcinoma of the mouse prostate)
Open this publication in new window or tab >>Epithelial cell apoptosis and decreases epithelial cell volume in TRAMP (transgenic adenocarcinoma of the mouse prostate)
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2005 (English)In: Nutrition and Cancer, ISSN 0163-5581, E-ISSN 1532-7914, Vol. 53, no 1, 111-116 p.Article in journal (Refereed) Published
Identifiers
urn:nbn:se:umu:diva-2677 (URN)
Available from: 2007-10-25 Created: 2007-10-25 Last updated: 2017-12-14Bibliographically approved
3. Anticancer effects of a plant lignan 7-hydroxymatairesinol on a prostate cancer model in vivo.
Open this publication in new window or tab >>Anticancer effects of a plant lignan 7-hydroxymatairesinol on a prostate cancer model in vivo.
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2005 (English)In: Experimental biology and medicine (Maywood, N.J.: Print), ISSN 1535-3702, E-ISSN 1535-3699, Vol. 230, no 3, 217-223 p.Article in journal (Refereed) Published
Abstract [en]

Clinical intervention studies and experimental studies with lignan-rich diets suggest that lignans may have inhibitory effects on prostate cancer, but no clinical or experimental studies with purified lignans have been published. The purpose of this study was to investigate the effect of a plant lignan 7-hydroxymatairesinol (HMR) on LNCaP human prostate cancer xenografts in athymic mice. Athymic nude male mice were injected subcutaneously with LNCaP cells. Starting 3 days after tumor cell injections, a control diet or a control diet supplemented with 0.15% or 0.30% of HMR was administered to mice and the tumor take rate and growth was observed for 9 weeks. HMR diet inhibited the growth of LNCaP tumors. Mice treated with HMR had smaller tumor volume, lower tumor take rate, increased proportion of nongrowing 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 diet. Our results suggest that dietary HMR started at the early phase of the tumor development inhibits the growth of the LNCaP human prostate cancer xenografts in athymic male mice.

Keyword
Phytoestrogens, 7-hydroxymatairesinol, diet, LNCaP human prostate adenocarcinoma, athymic nude mice
Identifiers
urn:nbn:se:umu:diva-14291 (URN)15734725 (PubMedID)
Available from: 2008-01-16 Created: 2008-01-16 Last updated: 2017-12-14Bibliographically approved
4. Randomised controlled short-term intervention pilot study on rye bran bread in prostate cancer.
Open this publication in new window or tab >>Randomised controlled short-term intervention pilot study on rye bran bread in prostate cancer.
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2003 (English)In: European Journal of Cancer Prevention, ISSN 0959-8278, E-ISSN 1473-5709, Vol. 12, no 5, 407-415 p.Article in journal (Refereed) Published
Keyword
Aged, Apoptosis, Bread, Cell Division, Dietary Fiber, Estrogens/pharmacokinetics, Gonadal Steroid Hormones/blood, Humans, Male, Middle Aged, Prostate-Specific Antigen/analysis, Prostatic Neoplasms/blood supply/*physiopathology/therapy, Secale cereale, Somatomedins/analysis, Weight Loss
Identifiers
urn:nbn:se:umu:diva-15175 (URN)14512806 (PubMedID)
Available from: 2007-11-23 Created: 2007-11-23 Last updated: 2017-12-14Bibliographically approved
5. Prospective study of plasma enterolactone and prostate cancer risk (Sweden).
Open this publication in new window or tab >>Prospective study of plasma enterolactone and prostate cancer risk (Sweden).
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2004 (English)In: Cancer Causes and Control, ISSN 0957-5243, E-ISSN 1573-7225, Vol. 15, no 10, 1095-1102 p.Article in journal (Refereed) Published
Keyword
4-Butyrolactone/*analogs & derivatives/*blood, Cohort Studies, Humans, Life Style, Lignans/*blood, Male, Middle Aged, Obesity/epidemiology, Phytoestrogens/*blood, Prospective Studies, Prostatic Neoplasms/blood/*epidemiology, Risk, Smoking/adverse effects, Sweden/epidemiology
Identifiers
urn:nbn:se:umu:diva-14216 (URN)10.1007/s10552-004-1480-7 (DOI)15801493 (PubMedID)
Available from: 2008-01-16 Created: 2008-01-16 Last updated: 2017-12-14Bibliographically approved

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