title: Inhibitory Effects of Enterolactone on Growth and Metastasis in Human Breast Cancer.
abstract: A lignan-rich diet is associated with a lower risk of human breast cancer. Enterolactone, an active polyphenol metabolites of lignan, was reported to have an antitumor effect. We investigated the mechanism for the effect of enterolactone against human breast cancer. Cellular changes, and associated genes induced by enterolactone, were investigated in MDA-MB-231 cells. Enterolactone showed an antiproliferative effect, and its IC50 was 261.9 ± 10.5 μM for a treatment period of 48 hr. The mRNA levels of the genes related to cell proliferation, Ki67, PCNA, and FoxM1, were reduced. Enterolactone induced accumulation of cells in the S phase, and a lower expression of Cyclin E1, Cyclin A2, Cyclin B1, and Cyclin B2 genes. There were almost no changes in the transcription levels of the genes that participate in G0/G1 phase regulation, CDK4, CDK6, and Cyclin D1. Furthermore, enterolactone interfered with the cytoskeleton by downregulating phosphorylation of the FAK/paxillin pathway, inhibiting migration and invasion of cells. The results suggest that enterolactone exerts an antitumor effect by regulating the expression of genes associated with cell proliferation and the cell cycle and by blocking the FAK/paxillin signaling pathway. These findings provide new insights into the molecular mechanisms behind the antitumor effect of enterolactone.
authors.affiliation: a State Key Laboratory of Food Science and Technology, Department of Life Science and Food Engineering, Nanchang University , Nanchang , China.|b Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Nanchang University , Nanchang , China.
authors.forename: Xiang-Yang
authors.initials: XY
authors.lastname: Xiong
authors.affiliation: b Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Nanchang University , Nanchang , China.
authors.forename: Xiao-Juan
authors.initials: XJ
authors.lastname: Hu
authors.affiliation: c The Institute of Translational Medicine, Nanchang University , Nanchang , China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.affiliation: a State Key Laboratory of Food Science and Technology, Department of Life Science and Food Engineering, Nanchang University , Nanchang , China.
authors.forename: Cheng-Mei
authors.initials: CM
authors.lastname: Liu
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000494:pharmacology; D001943:Breast Neoplasms / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects* / Q000235:genetics; D016213:Cyclins / Q000032:analysis / Q000235:genetics; D003599:Cytoskeleton / Q000187:drug effects; D051417:Focal Adhesion Kinase 1; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D019394:Ki-67 Antigen / Q000235:genetics; D017705:Lignans / Q000494:pharmacology*; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D051419:Paxillin; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D016196:S Phase; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D016213:Cyclins; C107585:FOXM1 protein, human; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors; D019394:Ki-67 Antigen; D017705:Lignans; D051419:Paxillin; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D015107:4-Butyrolactone; C029497:2,3-bis(3'-hydroxybenzyl)butyrolactone