Novel Lignan and stilbenoid mixture shows anticarcinogenic efficacy in preclinical PC-3M-luc2 prostate cancer model.

Prostate cancer is the most common cancer of men in the Western world, and novel approaches for prostate cancer risk reduction are needed. Plant-derived phenolic compounds attenuate prostate cancer growth in preclinical models by several mechanisms, which is in line with epidemiological findings suggesting that consumption of plant-based diets is associated with low risk of prostate cancer. The objective of this study was to assess the effects of a novel lignan-stilbenoid mixture in PC-3M-luc2 human prostate cancer cells in vitro and in orthotopic xenografts.

Estradiol, tamoxifen, and flaxseed alter IL-1β and IL-1Ra levels in normal human breast tissue in vivo.

Introduction: Sex steroid exposure increases the risk of breast cancer by unclear mechanisms. Diet modifications may be one breast cancer prevention strategy. The proinflammatory cytokine family of IL-1 is implicated in cancer progression.

Improved statistical modeling of tumor growth and treatment effect in preclinical animal studies with highly heterogeneous responses in vivo.

Purpose: Preclinical tumor growth experiments often result in heterogeneous datasets that include growing, regressing, or stable growth profiles in the treatment and control groups. Such confounding intertumor variability may mask the true treatment effects especially when less aggressive treatment alternatives are being evaluated.

Experimental Design: We developed a statistical modeling approach in which the growing and poorly growing tumor categories were automatically detected by means of an expectation-maximization algorithm coupled within a mixed-effects modeling framework.

Effect of dietary intervention on serum lignan levels in pregnant women - a controlled trial.

Background: Mother's diet during pregnancy is important, since plant lignans and their metabolites, converted by the intestinal microflora to enterolignans, are proposed to possess multiple health benefits. Aim of our study was to investigate whether a dietary intervention affects lignan concentrations in the serum of pregnant women.

Methods: A controlled dietary intervention trial including 105 first-time pregnant women was conducted in three intervention and three control maternity health clinics.

Flaxseed ingestion alters ratio of enterolactone enantiomers in human serum.

Enterolactone (EL) is an enterolignan found in human subjects. In this pilot study, the enantiomeric ratios of serum EL were determined in serum from healthy adults during consumption of habitual diet, and after an 8-day supplementation with flaxseed (25 g/day). (-)EL dominated in all serum samples collected during habitual diet consumption.

Prolonged administration of secoisolariciresinol diglycoside increases lignan excretion and alters lignan tissue distribution in adult male and female rats.

Limited information is available on lignan metabolism and tissue distribution between sexes and the effects of prolonged lignan exposure on tissue concentrations. In the present study, excretion and tissue distribution of lignans were compared after 1 d and 7 d administration of flaxseed lignan secoisolariciresinol diglycoside (SDG) in male and female rats. Sprague-Dawley rats were daily gavaged per os with 3H-SDG (3.

Assessment of information to substantiate a health claim on the prevention of prostate cancer by lignans.

Lignans and their in vivo metabolites, especially enterolactone (ENL), have attracted substantial interest as potential chemopreventive agents for prostate cancer. Preclinical and clinical interventions performed with lignan-rich flaxseed that use surrogate biomarkers as endpoints suggest that lignans may attenuate prostate carcinogenesis in individuals with increased risk or with diagnosed cancer. No unequivocal prostate cancer risk reduction has been found for lignans in epidemiological studies, suggesting that lignan concentrations found in populations consuming a regular non-supplemented diet are not chemopreventive in prostate cancer.

Estrogen-induced angiogenic factors derived from stromal and cancer cells are differently regulated by enterolactone and genistein in human breast cancer in vivo.

Angiogenesis is a key in cancer progression and its regulators are released both by the tumor cells and the stroma. Dietary phytoestrogens, such as the lignan enterolactone (ENL) and the isoflavone genistein (GEN), may differently affect breast cancer growth. In this study, human breast cancer cells (MCF-7) were established in mice creating a tumor with species-specific cancer and stroma cells.

Changes in biomarkers of estrogen receptor and growth factor signaling pathways in MCF-7 tumors after short- and long-term treatment with soy and flaxseed.

Previously we have shown that MCF-7 human breast tumor growth is stimulated after prolonged treatment with dietary soy protein isolate (SPI). However, the effects are attenuated when SPI is combined with flaxseed (FS). This study determined the changes that occur in tumor growth biomarkers, after both short- and long-term treatment with SPI, FS or their combination, to help identify signaling pathways potentially involved in SPI-stimulated tumor growth.

Dietary lariciresinol attenuates mammary tumor growth and reduces blood vessel density in human MCF-7 breast cancer xenografts and carcinogen-induced mammary tumors in rats.

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.

Lignans are accessible to human breast cancer xenografts in athymic mice.

Lignan-rich diet has been linked with reduced breast cancer risk, and experimental studies have supported the hypothesis of lignans as cancer growth inhibiting compounds. However, it has not been clear if these compounds are accessible in the mammary tumor tissue in vivo. In this study, the accessibility and accumulation of lignans to breast cancer tissue was determined after oral administration of tritium labeled dietary lignan secoisolariciresinol diglucoside (3H-SDG) to athymic mice bearing MCF-7 tumors.

Hydroxymatairesinol and sesaminol act differently on tocopherol concentrations in rats.

We have previously reported that sesame seed with the tetrahydrofurofuran type lignans sesamin and sesaminol (SeOH) produced higher tocopherol concentrations, while flaxseed with the dibenzylbutyrolactone type lignans did not cause higher tocopherol concentrations in rats. Sesame seeds also contain the dibenzylbutyrolactone type lignan 7-hydroxymatairesinol (HMR). To clarify whether or not the tocopherol elevating effect is affected by the chemical structure of lignans, the effect of HMR isolated from Norway spruce, was compared with SeOH, isolated from sesame seed.

Flaxseed and soy protein isolate, alone and in combination, differ in their effect on bone mass, biomechanical strength, and uterus in ovariectomized nude mice with MCF-7 human breast tumor xenografts.

In our previous study, flaxseed (FS) reduced while soy protein isolate (SPI) stimulated MCF-7 breast tumor growth in ovariectomized mice. In addition, combining SPI and FS resulted in a negation of SPI-induced tumor growth. In this study, the effects of SPI, FS, and their combination were further examined on mouse bone and uterus to further ensure overall safety of the breast cancer treatments.

Role of dietary lignans in the reduction of breast cancer risk.

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.

Hydroxymatairesinol and its mammalian metabolite enterolactone reduce the growth and metastasis of subcutaneous AH109A hepatomas in rats.

Both epidemiological and experimental evidence is accumulating to show that a lignan-rich diet may reduce the risk of human breast cancer. Possible anti-cancer effects of dietary lignans on hepatomas or hepatoma cells have not been the topic of earlier studies. In the present study, we examined the effect of 7-hydroxymatairesinol (HMR) and its mammalian metabolite, enterolactone (ENL), on AH109A hepatoma cell proliferation and invasion in vitro.

Can modulation of mammary gland development by dietary factors support breast cancer prevention?

Breast cancer continues to be a major challenge for public health, since it is the most common cancer of women in the Western world, and its prevalence is still increasing. In order to achieve better results in the prevention and treatment of breast cancer it is crucial to identify the mechanisms behind its initiation, i.e.

Flaxseed attenuates the tumor growth stimulating effect of soy protein in ovariectomized athymic mice with MCF-7 human breast cancer xenografts.

In several epidemiological studies, a phytoestrogen-rich diet containing lignans and isoflavones is associated with reduced breast cancer risk, but experimental findings are controversial. In postmenopausal mammary cancer xenograft model, flaxseed (FS), a rich source of plant lignans, reduced breast cancer growth, while soy protein (SP), a rich source of isoflavones, enhanced it. The intake of phytoestrogens is increasing particularly among postmenopausal women, emphasizing the importance of elucidating their interactive effects on breast cancer.

Sesamin is one of the major precursors of mammalian lignans in sesame seed (Sesamum indicum) as observed in vitro and in rats.

Plant lignans occur in many foods, with flaxseed presently recognized as the richest source. Some plant lignans can be converted by intestinal microbiota to the mammalian lignans, enterodiol and enterolactone, which may have protective effects against hormone-related diseases such as breast cancer. This study determined whether plant lignans in sesame seed, particularly sesamin, could be metabolized to the mammalian lignans.

Genistein alone and in combination with the mammalian lignans enterolactone and enterodiol induce estrogenic effects on bone and uterus in a postmenopausal breast cancer mouse model.

The use of phytoestrogens, such as isoflavones and lignans, for treatment of postmenopausal breast cancer is increasing, but their effects on bone and other major organs are not clear. While the isoflavone genistein (GEN) has been shown to prevent or slow the loss of bone mineral density (BMD), the effect of lignans enterodiol (END) and enterolactone (ENL) are unknown. In this study, we determined in ovariectomized mice with human MCF-7 breast tumor xenografts the effects of the lignans, and GEN, alone and in combination, on bone and uterus.

Determination of plant and enterolignans in human serum by high-performance liquid chromatography with tandem mass spectrometric detection.

An HPLC-MS/MS method was validated for the determination of the plant lignans 7-hydroxymatairesinol (HMR), matairesinol (Mat), secoisolariciresinol (Seco), lariciresinol (Lar), and cyclolariciresinol (CLar) and for the enterolignans 7-hydroxyenterolactone (HEL), enterodiol (ED), and enterolactone (EL) in human serum. The method included sample enzymatic hydrolysis, solid-phase extraction, and lignan analysis using a triple quadrupole mass spectrometer with electrospray ionisation in the multiple-reaction monitoring mode. The serum lignans were quantified using deuterated Mat or EL as internal standards.

Mammalian lignans enterolactone and enterodiol, alone and in combination with the isoflavone genistein, do not promote the growth of MCF-7 xenografts in ovariectomized athymic nude mice.

This study determined the effect of the mammalian lignans enterolactone (ENL) and enterodiol (END) alone and in combination with the isoflavone genistein (GEN) on the growth of MCF-7 tumors in ovariectomized nude mice. Ovariectomized athymic nude mice with established MCF-7 tumors were fed a basal diet (AIN-93G) and divided into 5 groups that received daily subcutaneous injections (10 mg/kg body weight (BW)) of ENL, END, GEN, a mixture of these compounds (MIX), or vehicle as a negative control for 22 weeks. A positive control group was implanted with an estradiol pellet in order to establish an estrogenic tumor growth response.

New lignan metabolites in rat urine.

Ten potential lignan metabolites were quantified in rat urine extracts using liquid chromatography-tandem mass spectrometry. The rats were orally administered with the plant lignans 7-hydroxymatairesinol, matairesinol, lariciresinol or secoisolariciresinol, or with the mammalian lignan enterolactone. The samples were enzymatically hydrolysed and solid-phase extracted before analysis.

Urinary excretion of lignans after administration of isolated plant lignans to rats: the effect of single dose and ten-day exposures.

The difference in urinary excretion of mammalian and plant lignans in rats was determined after oral administration of equivalent doses (25 mg/kg of body weight) of 7-hydroxymatairesinol (HMR), lariciresinol (LAR), matairesinol (MR), and secoisolariciresinol (SECO). Twenty-four hours-urine samples were collected after a single dose and after administration of one dose/day for 10 days. Eight lignans were analysed in urine extracts using a high-performance liquid chromatography-tandem mass spectrometry method showing good sensitivity and repeatability.

Enterolactone inhibits the growth of 7,12-dimethylbenz(a)anthracene-induced mammary carcinomas in the rat.

The inverse association between a high enterolactone (ENL) concentration in both urine and serum, and the risk of breast cancer found in epidemiological studies suggests a chemopreventive action for ENL. However, no causal relationship has been established in clinical studies or in experimental models for breast cancer. In the present study, the potential chemopreventive action of p.

Structural determinants of plant lignans for the formation of enterolactone in vivo.

The quantity of mammalian lignans enterolactone (ENL) and enterodiol (END) and of plant lignans secoisolariciresinol (SECO) and 7-hydroxymatairesinol (HMR) excreted in a 24-h rat urine sample was measured after a single p.o. dose of an equivalent quantity of secoisolariciresinol diglycoside (SDG), secoisolariciresinol (SECO), matairesinol (MR), 7-hydroxymatairesinol (HMR) and ENL.