How lignans fight cancer?

http://nutraprointl.com/2009/12/25/how-lignans-fight-cancer/ 

 Lignans are naturally occurring compounds found in plants. Lignans are one of the major classes of phytoestrogens. When part of our diet, bacteria in our intestines (colon) convert the naturally occurring dietary phytoestrogens into mammalian lignans known as enterodiol and enterolactone (Figure 1; Wang, 2002;  J Chromatogr B Analyt Technol Biomed Life Sci. 2002 Sep 25;777(1-2):289-309).

These are the biologically active lignans that are transported across the intestinal wall into the blood. Lignans that can be metabolized to form mammalian lignans are pinoresinol, lariciresinol, secoisolariciresinol, matairesinol, hydroxymatairesinol, syringaresinol and sesamin.

Flax seed and sesame seed have the highest levels of lignans. The major lignin precursor found in flax seed is secoisolariciresinol diglucoside. Other sources of lignans are rye, wheat, oat, barley, pumpkin seeds, soybeans, broccoli, beans, and some berries.

Flaxseed contains the highest concentrations of lignan precursors than any other plant. Most people don’t eat flax seed. They eat other grains that contain much less lignans than flax seed. The more flax seed you consume, the more lignans enter the body.

Lignans are being studied for possible use in cancer prevention, particularly breast cancer. Lignans acts as anticancer compounds by blocking powerful growth factor receptors like epidermal growth factor (EGF), Her2, Insulin like growth factor-1, and vascular endothelial growth factor (VEGF), the hormone responsible for stimulating blood vessels into tumors. The lignans are incredibly effective at blocking estrogen II receptors at very low doses. Below are some scientific evidences:

In a following study, women newly diagnosed with breast cancer were given a daily single muffin to eat that contained 25 grams of flax seeds. Controls got a wheat muffin. After a little more than 30 days, the women eating the single muffin per day saw the cell growth index of their breast cancer cells decrease by 34%.

Dietary flaxseed alters tumor biological markers in postmenopausal breast cancer.
Thompson LU, Chen JM, Li T, Strasser-Weippl K, Goss PE.
Clin Cancer Res. 2005 May 15;11(10):3828-35
Flaxseed, the richest source of mammalian lignan precursors, has previously been shown to reduce the growth of tumors in rats. This study examined, in a randomized double-blind placebo-controlled clinical trial, the effects of dietary flaxseed on tumor biological markers and urinary lignan excretion in postmenopausal patients with newly diagnosed breast cancer. Patients were randomized to daily intake of either a 25 g flaxseed-containing muffin (n = 19) or a control (placebo) muffin (n = 13). At the time of diagnosis and again at definitive surgery, tumor tissue was analyzed for the rate of tumor cell proliferation (Ki-67 labeling index, primary end point), apoptosis, c-erbB2 expression, and estrogen and progesterone receptor levels. Twenty-four-hour urine samples were analyzed for lignans, and 3-day diet records were evaluated for macronutrient and caloric intake. Mean treatment times were 39 and 32 days in the placebo and flaxseed groups, respectively. RESULTS: Reductions in Ki-67 labeling index (34.2%; P = 0.001) and in c-erbB2 expression (71.0%; P = 0.003) and an increase in apoptosis (30.7%; P = 0.007) were observed in the flaxseed, but not in the placebo group. No significant differences in caloric and macronutrient intake were seen between groups and between pre- and posttreatment periods. A significant increase in mean urinary lignan excretion was observed in the flaxseed group (1,300%; P < 0.01) compared with placebo controls. The total intake of flaxseed was correlated with changes in c-erbB2 score (r = -0.373; P = 0.036) and apoptotic index (r = 0.495; P < 0.004). CONCLUSION: Dietary flaxseed has the potential to reduce tumor growth in patients with breast cancer.

Flaxseed inhibits metastasis and decreases extracellular vascular endothelial growth factor in human breast cancer xenografts.Dabrosin C, Chen J, Wang L, Thompson LU.

Cancer Lett . 2002 Nov 8;185(1):31-7.

Angiogenesis is important in tumor growth, progression and metastatic dissemination. Vascular endothelial growth factor (VEGF) is one key factor in promotion of breast cancer angiogenesis. VEGFs are bioactive in the extracellular space where they become available to the endothelial cells. Phytoestrogens such as lignans have been shown to alter breast cancer incidence and be cancer-protective in rats. We show that supplementation of 10% flaxseed, the richest source of mammalian lignans, to nude mice with established human breast tumors reduced tumor growth and metastasis. Moreover, flaxseed decreased extracellular levels of VEGF, which may be one mechanistic explanation to the decreased tumor growth and metastasis.

Flaxseed products were shown to reduce the metastasis of melanoma cells, one of the MOST metastatic of all cancers.

Dietary supplementation with secoisolariciresinol diglycoside (SDG) reduces experimental metastasis of melanoma cells in mice.
Li D, Yee JA, Thompson LU, Yan L.

Cancer Lett. 1999 Jul 19;142(1):91-6.

We investigated the effect of dietary supplementation with secoisolariciresinol diglycoside (SDG), a lignan precursor isolated from flaxseed, on experimental metastasis of B16BL6 murine melanoma cells in C57BL/6 mice. Four diets were compared: a basal diet (control group) and the basal diet supplemented with SDG at 73, 147 or 293 micromol/kg (equivalent to SDG provided in the 2.5, 5 or 10% flaxseed diet). Mice were fed the diet for 2 weeks before and after an intravenous injection of 0.6 x 10(5) tumor cells. At necropsy, the number and size of tumors that formed in the lungs were determined. The median number of tumors in the control group was 62, and those in the SDG-supplemented groups were 38, 36 and 29, respectively. The last was significantly different from the control (P < 0.01). Dietary supplementation with SDG at 73, 147 and 293 micromol/kg also decreased tumor size (tumor cross-sectional area and volume) in a dose-dependent manner compared with the control values. These results show that SDG reduced pulmonary metastasis of melanoma cells and inhibited the growth of metastatic tumors that formed in the lungs. It is concluded that dietary supplementation with SDG reduces experimental metastasis of melanoma cells in mice.

The Canadian team investigated the association between dietary phytoestrogen intake (isoflavones, lignans and total phytoestrogens) and colorectal cancer risk among cases (aged 20-74 yrs). Of all the cases and controls approached, 1095 cases and 1890 controls completed epidemiological as well as food-frequency questionnaires. And 842 cases and 1251 controls gave blood samples for tracking any genetic roles in phytoestrogen metabolism and incidence of colorectal cancer.

Researchers found a link between higher phytoestrogen intake (lignans and isoflavones combined) and reduced risk of colorectal cancer. No significant roles of genes were found in association between phytoestrogen metabolism and colorectal cancer risk. Studies with human colon cancer cells (SW480) have shown that lignans thwart the growth of tumor cells driving them to commit mass suicide (apoptosis).

Dietary Phytoestrogen Intake Is Associated with Reduced Colorectal Cancer Risk. Michelle Cotterchio, Beatrice A. Boucher, Michael Manno, Steven Gallinger, Allan Okey and Patricia Harper

J. Nutr. 136:3046-3053, December 2006

Evidence suggests dietary phytoestrogens may reduce the risk of certain hormonal cancers (e.g. breast and prostate). Thereis a paucity of data regarding phytoestrogens and colorectal cancer risk. Phytoestrogens are plant compounds with estrogen-like activities. Main classes include isoflavones (found in legumes such as soy) and lignans (found in grains, seeds, nuts, fruits, and vegetables). Although isoflavones have dominated phytoestrogen cancer research, lignans may be more relevant to North American diets. Food questionnaires and analytic databases have recently been modified to incorporate some lignan information. We conducted a case-control study to evaluate the association between phytoestrogen intake and colorectal cancer risk. Colorectal cancer cases were diagnosed in 1997–2000, aged 20–74 y, identified through the population-based Ontario Cancer Registry, and recruited by the Ontario Familial Colorectal Cancer Registry. Controls were a sex and age-group matched random sample of the population of Ontario. Epidemiologic and food frequency questionnaires were completed by 1095 cases and 1890 control subjects. Multivariate logistic regression analysis was used to obtain adjusted odds ratio (OR) estimates. Dietary lignan intake was associated with a significant reduction in colorectal cancer risk [OR (T3 vs.T1) = 0.73; 95% CI: 0.56, 0.94], as was isoflavone intake [OR (T3 vs. T1) = 0.71; 95% CI: 0.58, 0.86]. We evaluated interactions between polymorphic genes that encode enzymes possibly involved in metabolism of phytoestrogens (CYPs, catechol O-methyl transferase,GSTs, and UGTs) and found no significant effect modification with respect to phytoestrogen intake. This finding that phytoestrogen intake may reduce colorectal cancer risk is important, because dietary intake is potentially modifiable.

Colorectal cancer is the third most common cancer and the third leading cause of cancer related mortality in the United States. According to the National Cancer Institute, in 2007, 112,340 new cases of colon cancer and 41,420 cases of rectal cancer have been detected with 52,180 deaths from colorectal cancer.

We promote healthy lifestyle through natural foods. An inexpensive but amazing flax seed works powerfully against breast cancer. Flax seed is available in some grocery stores in the United States and in almost all health food stores.  

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