Flaxseed-Derived Enterolactone Is Inversely Associated with Tumor Cell Proliferation in Men with Localized Prostate Cancer

다국어 초록 (Multilingual Abstract)

Enterolactone and enterodiol, mammalian lignans derived from dietary sources such as flaxseed, sesame seeds, kale, broccoli, and apricots, may impede tumor proliferation by inhibiting activation of nuclear factor kappa B (NFκB) and vascular endothelial growth factor (VEGF). We examined the associations between urinary enterolactone and enterodiol with prostatic tumor expression of NFκB, VEGF, and Ki67 among 147 patients with prostate cancer who participated in a presurgical trial of flaxseed supplementation (30 g/day) for 30 days. Urinary enterolignans and tissue biomarkers were determined by high-performance liquid chromatography and immunohistochemistry, respectively. After supplementation, we observed significant correlations between intakes of plant lignan and urinary concentrations of total enterolignans (ρ=0.677, P<.0001), enterolactone (ρ=0.676, P<.0001), and enterodiol (ρ=0.628, P<.0001). Importantly, we observed that total urinary enterolignans and enterolactone were significantly and inversely correlated with Ki67 in the tumor tissue (ρ=−0.217, P=.011, and ρ=−0.230, P=.007, respectively), and a near-significant inverse association was observed for enterodiol (ρ=−0.159, P=.064). An inverse association was observed between enterolactone and VEGF (ρ=−0.143, P=.141), although this did not reach statistical significance. We did not observe an association between enterolignans and NFκB. In conclusion, flaxseed-derived enterolignans may hinder cancer cell proliferation via VEGF-associated pathways.

참고문헌 (Reference)

1 A ° berg UW, "Tamoxifen and flaxseed alter angiogenesis regulators in normal human breast tissue in vivo" 6 : e25720-, 2011

2 Buck K, "Serum enterolactone and prognosis of postmenopausal breast cancer" 29 : 3730-3738, 2011

3 Fabian CJ, "Reduction in Ki-67 in benign breast tissue of high-risk women with the lignan secoisolariciresinol diglycoside" 3 : 1342-1350, 2010

4 Borriello SP, "Production and metabolism of lignans by the human faecal flora" 58 : 37-43, 1985

5 Adlercreutz H, "Phytoestrogens: epidemiology and a possible role in cancer protection" 103 (103): 103-112, 1995

6 Thompson LU, "Phytoestrogen content of foods consumed in Canada, including isoflavones, lignans, and coumestan" 54 : 184-201, 2006

7 Grace PB, "Phytoestrogen concentrations in serum and spot urine as biomarkers for dietary phytoestrogen intake and their relation to breast cancer risk in European prospective investigation of cancer and nutritionnorfolk" 13 : 698-708, 2004

8 Heald CL, "Phyto-oestrogens and risk of prostate cancer in Scottish men" 98 : 388-396, 2007

9 Hanahan D, "Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis" 86 : 353-364, 1996

10 Nam NH, "Naturally occurring NF-kappaB inhibitors" 6 : 945-951, 2006

11 Buck K, "Meta-analyses of lignans and enterolignans in relation to breast cancer risk" 92 : 141-153, 2010

12 Morton MS, "Lignans and isoflavonoids in plasma and prostatic fluid in men: samples from Portugal, Hong Kong, and the United Kingdom" 32 : 122-128, 1997

13 Adolphe JL, "Health effects with consumption of the flax lignan secoisolariciresinol diglucoside" 103 : 929-938, 2010

14 Hanahan D, "Hallmarks of cancer: the next generation" 144 : 646-674, 2011

15 Thompson L, "Flaxseed, Lignans, and Cancer" AOCS Press 194-222, 2004

16 Demark-Wahnefried W, "Flaxseed supplementation (not dietary fat restriction) reduces prostate cancer proliferation rates in men presurgery" 17 : 3577-3587, 2008

17 Dabrosin C, "Flaxseed inhibits metastasis and decreases extracellular vascular endothelial growth factor in human breast cancer xenografts" 185 : 31-37, 2002

18 Bergman Jungestro¨m M, "Flaxseed and its lignans inhibit estradiol-induced growth, angiogenesis, and secretion of vascular endothelial growth factor in human breast cancer xenografts in vivo" 13 : 1061-1067, 2007

19 Corsini E, "Enterodiol and enterolactone modulate the immune response by acting on nuclear factor-kappaB (NF-kappaB) signaling" 58 : 6678-6684, 2010

20 Heymach JV, "Effect of low-fat diet on plasma levels of NF-{kappa}B-regulated inflammatory cytokines and angiogenic factors in men with prostate cancer" 4 : 1590-1598, 2011

21 Hedelin M, "Dietary phytoestrogen, serum enterolactone and risk of prostate cancer: the cancer prostate Sweden study (Sweden)" 17 : 169-180, 2006

22 McCann SE, "Dietary intakes of total and specific lignans are associated with clinical breast tumor characteristics" 142 : 91-98, 2012

23 Thompson LU, "Dietary flaxseed alters tumor biological markers in postmenopausal breast cancer" 11 : 3828-3825, 2005

24 Subar AF, "Comparative validation of the Block, Willett, and National Cancer Institute food frequency questionnaires: the Eating at America’s Table Study" 154 : 1089-1099, 2001