title: Flaxseed-derived enterolactone is inversely associated with tumor cell proliferation in men with localized prostate cancer.
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.
authors.affiliation: Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA. maria123@uab.edu
authors.forename: Maria
authors.initials: M
authors.lastname: Azrad
authors.forename: Robin T
authors.initials: RT
authors.lastname: Vollmer
authors.forename: John
authors.initials: J
authors.lastname: Madden
authors.forename: Mark
authors.initials: M
authors.lastname: Dewhirst
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Polascik
authors.forename: Denise C
authors.initials: DC
authors.lastname: Snyder
authors.forename: Mack T
authors.initials: MT
authors.lastname: Ruffin
authors.forename: Judd W
authors.initials: JW
authors.lastname: Moul
authors.forename: Dean E
authors.initials: DE
authors.lastname: Brenner
authors.forename: Wendy
authors.initials: W
authors.lastname: Demark-Wahnefried
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use / Q000652:urine; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism / Q000652:urine; D049109:Cell Proliferation / Q000187:drug effects; D019587:Dietary Supplements; D019597:Flax / Q000737:chemistry*; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D017705:Lignans / Q000494:pharmacology / Q000627:therapeutic use* / Q000652:urine; D008297:Male; D008875:Middle Aged; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000652:urine; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D015415:Biomarkers; D019394:Ki-67 Antigen; D017705:Lignans; D010936:Plant Extracts; D042461:Vascular Endothelial Growth Factor A; C029498:2,3-bis(3'-hydroxybenzyl)butane-1,4-diol; D015107:4-Butyrolactone; C029497:2,3-bis(3'-hydroxybenzyl)butyrolactone