title: Docosahexaenoic acid suppresses breast cancer cell metastasis by targeting matrix-metalloproteinases.
abstract: Breast cancer is one of the most prevalent cancers in women, and nearly half of breast cancer patients develop distant metastatic disease after therapy. Despite the significant advances that have been achieved in understanding breast cancer metastasis in the past decades, metastatic cancer is still hard to cure. Here, we demonstrated an anti-cancer mechanism of docosahexaenoic acid (DHA) that suppressed lung metastasis in breast cancer. DHA could inhibit proliferation and invasion of breast cancer cells in vitro, and this was mainly through blocking Cox-2-PGE2-NF-κB-MMPs cascades. DHA treatment significantly decreased Cox-2 and NF-κB expression as well as nuclear translocation of NF-κB in MDA-MB-231 cells. In addition, DHA also reduced NF-κB binding to DNA which may lead to inactivation of MMPs. Moreover, in vivo studies using Fat-1 transgenic mice showed remarkable decrease of tumor growth and metastasis to EO771 cells to lung in DHA-rich environment. In conclusion, DHA attenuated breast cancer progression and lung metastasis in part through suppressing MMPs, and these findings suggest chemoprevention and potential therapeutic strategy to overcome malignant breast cancer.
authors.affiliation: Department of Biochemistry, College of Medicine, Chungnam National University, Daejon 301-747, Republic of Korea.|Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Eun-Jin
authors.initials: EJ
authors.lastname: Yun
authors.affiliation: Department of Biochemistry, College of Medicine, Chungnam National University, Daejon 301-747, Republic of Korea.|Department of Pathology and Laboratory Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA.
authors.forename: Kyung-Sub
authors.initials: KS
authors.lastname: Song
authors.affiliation: Department of Biochemistry, College of Medicine, Chungnam National University, Daejon 301-747, Republic of Korea.
authors.forename: Soyeon
authors.initials: S
authors.lastname: Shin
authors.affiliation: Department of Biochemistry, College of Medicine, Chungnam National University, Daejon 301-747, Republic of Korea.
authors.forename: Soyeon
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, College of Medicine, Chungnam National University, Daejon 301-747, Republic of Korea.
authors.forename: Jun-Young
authors.initials: JY
authors.lastname: Heo
authors.affiliation: Department of Biochemistry, College of Medicine, Chungnam National University, Daejon 301-747, Republic of Korea.|Infection Signaling Network Research Center, Chungnam National University, Daejon 301-747, Republic of Korea.
authors.forename: Gi-Ryang
authors.initials: GR
authors.lastname: Kweon
authors.affiliation: Department of Pathology and Laboratory Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA.
authors.forename: Tong
authors.initials: T
authors.lastname: Wu
authors.affiliation: Department of Biochemistry, College of Medicine, Chungnam National University, Daejon 301-747, Republic of Korea.
authors.forename: Jong-Il
authors.initials: JI
authors.lastname: Park
authors.affiliation: Department of Biochemistry, College of Medicine, Chungnam National University, Daejon 301-747, Republic of Korea.|Infection Signaling Network Research Center, Chungnam National University, Daejon 301-747, Republic of Korea.|Cancer Research Institute, Chungnam National University, Daejon 301-747, Republic of Korea.
authors.forename: Kyu
authors.initials: K
authors.lastname: Lim
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D017209:Apoptosis; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D017077:Culture Media, Conditioned; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000037:antagonists & inhibitors; D018450:Disease Progression; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis / Q000517:prevention & control*
chemical_list: D017077:Culture Media, Conditioned; D061965:Matrix Metalloproteinase Inhibitors; D016328:NF-kappa B; D004281:Docosahexaenoic Acids; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; D015232:Dinoprostone
keywords: DHA; MMP; breast cancer; omega-3 PUFA