Structural determinants of plant lignans for growth of mammary tumors and hormonal responses in vivo (original) (raw)
Related papers
Role of dietary lignans in the reduction of breast cancer risk
Molecular nutrition & food research, 2007
Lignans are a large group of fiber-associated phenolic compounds widely distributed in edible plants. Some of the ingested plant lignans are converted by intestinal microbiota to enterolignans, enterodiol (END) and enterolactone (ENL), the latter of which has been thought to be the major biologically active lignan, and suggested to be associated with low risk of breast cancer. In line with this, administration of plant lignans which are further metabolized to ENL, or ENL as such, have been shown to inhibit or delay the growth of experimental mammary cancer. The mechanism of anticarcinogenic action of ENL is not yet fully understood, but there is intriguing evidence for ENL as a modulator of estrogen signaling. These findings have generated interest in the use of lignans as components of breast cancer risk reducing functional foods. Identification of target groups, who would benefit most, is of pivotal importance. Therefore, further identification and validation of relevant biomarker...
9Experimental studies on lignans and cancer
Baillière's Clinical Endocrinology and Metabolism, 1998
Mammalian lignans are produced from plant precursors such as secoisolariciresinol diglycoside (SDG) and matairesinol via the action of bacteria in the human or animal colon. While precursors are found in many plant foods, flaxseed is the richest source of SDG and was therefore used as a model to determine the anti-cancer effects of lignans. This paper reviews the experimental studies in animals and humans demonstrating the anti-cancer effects of flaxseed and its SDG as well as other studies relevant to the clinical use of lignans, such as those on their food sources, bio-availability and safety.
Inhibition of human aromatase by mammalian lignans and isoflavonoid phytoestrogens
Journal of Steroid Biochemistry and Molecular Biology, 1993
Snmmary--Isoflavonoid phytoestrogens and lignans in plants are known to be constituents of animal and human food and recently they have been found in human urine and other biological materials. These compounds have received increasing attention because of their interesting biological properties and possible role in human cancer and other diseases. The present study demonstrates that the main mammalian fignan enterolactone (trans-2,3-bis[(3hydroxyphenyl)methyl]-butyrolactone) and some other diphenols are moderate or weak inhibitors of human estrogen synthetase (aromatase) and that this lignan binds to or near the substrate region of the active site of the P-450 enzyme. The inhibition is competitive with respect to testosterone and androstenedione, and the lignan aifudty is 1/75-1/300 that of these natural substrates. It is suggested that the high concentration of lignans in vegetarians, by inhibiting aromatase in peripheral and/or cancer cells and lowering estrogen levels, may play a protective role as antipromotional compounds during growth of estrogen-dependent cancers.
Journal of AOAC INTERNATIONAL, 2007
Lignans in flaxseed have been part of the human diet for centuries. In 1955, the isolation and structure of the lignan derivative secoisolariciresinol diglucoside (SDG) was reported. The biological role of SDG and mammalian lignan metabolites enterodiol and enterolactone was initially reported 20 years later. Experimental evidences showed the beneficial effects of lignans on breast, colon, and thyroid cancer. A modified gas chromatography/mass spectrometry (GC/MS) assay was developed for lignans in serum and colon samples of rats fed flaxseed meal. The method developed for the analysis of metabolites involves extraction and derivatization of samples and quantitative analysis by selected ion monitoring using GC/MS. The levels of lignan metabolites enterodiol and enterolactone were determined to be 0.013 and 0.23 M in serum samples and 0.008 and 1.63 M in colon samples.
Role of mammalian lignans in the prevention and treatment of prostate cancer
Nutrition and cancer, 2005
Prostate cancer is poised to become the most prevalent male cancer in the Western world. In Japan and China, incidence rates are almost 10-fold less those reported in the United States and the European Union. Epidemiological data suggest that environmental factors such as diet can significantly influence the incidence and mortality of prostate cancer. The differences in lifestyle between East and West are one of the major risk factors for developing prostate cancer. Traditional Japanese and Chinese diets are rich in foods containing phytoestrogenic compounds, whereas the Western diet is a poor source of these phytochemicals. The lignan phytoestrogens are the most widely occurring of these compounds. In vitro and in vivo reports in the literature indicate that lignans have the capacity to affect the pathogenesis of prostate cancer. However, their precise mechanism of action in prostate carcinogenesis remains unclear. This article outlines the possible role of lignans in prostate cancer by reviewing the current in vitro and in vivo evidence for their anticancer activities. The intriguing concept that lignans may play a role in the prevention and treatment of prostate cancer over the lifetime of an individual is discussed.
The Journal of Nutrition, 2011
Dietary lignans may affect breast cancer by modifying tumor characteristics likely to affect prognosis. We investigated usual dietary intakes of total and specific lignans with tumor characteristics in 683 women with breast cancer and 611 healthy women without breast cancer enrolled in the Data Bank and BioRepository at Roswell Park Cancer Institute (RPCI). Clinicopathologic data were abstracted from the RPCI breast cancer database. Dietary lignan intakes were calculated from FFQ. OR and 95% CI were estimated with logistic regression adjusting for potential confounders and stratified by menopausal status. Women in the highest compared to the lowest tertile of total lignan intakes had a 40-50% lower odds of breast cancer regardless of menopausal status and substantially reduced odds of an invasive tumor, especially among premenopausal women [OR 0.48 (95% CI 0.26-0.86)]. Lignan intakes were inversely associated with odds of grade 3 tumors among premenopausal women. Lignan intakes were inversely associated with risk of estrogen receptor (ER) negative (ER 2) breast cancer among premenopausal women [OR 0.16 (95% CI 0.03-0.44)] and particularly triple negative tumors [ER 2 , progesterone receptor negative, HER2 negative; OR 0.16 (95% CI 0.04-0.62)]. There were significant differences in the contribution to these effects by specific lignans, especially matairesinol and lariciresinol. In summary, in this case-control study of dietary lignan intakes and breast cancer, we found that higher lignan intakes were associated with lower risks of breast cancer with more favorable prognostic characteristics. Future investigations are warranted to explore the strong associations observed with ER 2 cancer in premenopausal women. J. Nutr. 142: 91-98, 2012.
Journal of Nutrition, 2012
Dietary lignans may affect breast cancer by modifying tumor characteristics likely to affect prognosis. We investigated usual dietary intakes of total and specific lignans with tumor characteristics in 683 women with breast cancer and 611 healthy women without breast cancer enrolled in the Data Bank and BioRepository at Roswell Park Cancer Institute (RPCI). Clinicopathologic data were abstracted from the RPCI breast cancer database. Dietary lignan intakes were calculated from FFQ. OR and 95% CI were estimated with logistic regression adjusting for potential confounders and stratified by menopausal status. Women in the highest compared to the lowest tertile of total lignan intakes had a 40-50% lower odds of breast cancer regardless of menopausal status and substantially reduced odds of an invasive tumor, especially among premenopausal women [OR 0.48 (95% CI 0.26-0.86)]. Lignan intakes were inversely associated with odds of grade 3 tumors among premenopausal women. Lignan intakes were inversely associated with risk of estrogen receptor (ER) negative (ER 2 ) breast cancer among premenopausal women [OR 0.16 (95% CI 0.03-0.44)] and particularly triple negative tumors [ER 2 , progesterone receptor negative, HER2 negative; OR 0.16 (95% CI 0.04-0.62)]. There were significant differences in the contribution to these effects by specific lignans, especially matairesinol and lariciresinol. In summary, in this case-control study of dietary lignan intakes and breast cancer, we found that higher lignan intakes were associated with lower risks of breast cancer with more favorable prognostic characteristics. Future investigations are warranted to explore the strong associations observed with ER 2 cancer in premenopausal women. J. Nutr. 142: 91-98, 2012.
International Journal of Cancer, 2008
Lariciresinol is a dietary lignan that accounts for a significant portion of the total phytoestrogen intake from Western foods. Recent epidemiological studies suggest that high dietary intake of lignans and lariciresinol is associated with reduced breast cancer risk. However, no causal relationship between lariciresinol intake and breast cancer development has been established. In this study, we investigated for the first time the effects and possible mechanisms of action of lariciresinol on hormone responsive mammary cancer in vivo in dimethylbenz[a]anthracene induced mammary cancer in rats, and in human MCF-7 breast cancer xenografts in athymic mice. For tumor bearing rats, lariciresinol (3 or 15 mg/kg of body weight) or vehicle was administered p.o. daily for 9 weeks. For E2-maintained ovariectomized athymic mice bearing orthotopic MCF-7 tumors, control diet (AIN-93G) or lariciresinol containing diet (AIN-93G supplemented with 20 or 100 mg of lariciresinol/kg of diet) was administered for 5 weeks. In both models, lariciresinol administration inhibited the tumor growth and tumor angiogenesis. In MCF-7 cells, enterolactone significantly inhibited the E2-stimulated VEGF secretion. Moreover, in MCF-7 xenografts, lariciresinol administration enhanced tumor cell apoptosis and increased estrogen receptor beta expression. Lariciresinol and its further metabolites secoisolariciresinol, enterodiol and enterolactone were found in serum of both rats and athymic mice confirming a similar lignan metabolism pattern as in humans. These findings indicate conceivable importance of dietary lignan lariciresinol in inhibition of breast cancer development.