Docosahexaenoic acid suppresses breast cancer cell metastasis by targeting matrix-metalloproteinases

// Eun-Jin Yun 1, 4, * , Kyung-Sub Song 1, 5, * , Soyeon Shin 1 , Soyeon Kim 1 , Jun-Young Heo 1 , Gi-Ryang Kweon 1, 2 , Tong Wu 5 , Jong-Il Park 1 , Kyu Lim 1, 2, 3 1 Department of Biochemistry, College of Medicine, Chungnam National University, Daejon 301-747, Republic of Korea 2 Infection Signaling Network Research Center, Chungnam National University, Daejon 301-747, Republic of Korea 3 Cancer Research Institute, Chungnam National University, Daejon 301-747, Republic of Korea 4 Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA 5 Department of Pathology and Laboratory Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA * These authors have contributed equally to this work Correspondence to: Jong-Il Park, email: jipark@cnu.ac.kr Kyu Lim, email: kyulim@cnu.ac.kr Keywords: DHA, omega-3 PUFA, MMP, breast cancer Received: August 07, 2015      Accepted: April 07, 2016      Published: June 23, 2016 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-PGE 2 -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.