Brown Seaweed Fucoidan Inhibits Cancer Progression by Dual Regulation of mir-29c/ADAM12 and miR-17-5p/PTEN Axes in Human Breast Cancer Cells

Szu-Yuan Wu; Alexander T H Wu; Kevin Sheng-Po Yuan; Shing Hwa Liu

doi:10.7150/jca.15703

Brown Seaweed Fucoidan Inhibits Cancer Progression by Dual Regulation of mir-29c/ADAM12 and miR-17-5p/PTEN Axes in Human Breast Cancer Cells

J Cancer. 2016 Dec 9;7(15):2408-2419. doi: 10.7150/jca.15703. eCollection 2016.

Authors

Szu-Yuan Wu¹, Alexander T H Wu², Kevin Sheng-Po Yuan³, Shing Hwa Liu⁴

Affiliations

¹ Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan;; Department of Radiation Oncology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan;; Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan;; Department of Biotechnology, Hungkuang University, Taichung, Taiwan.
² Department of Otorhinolaryngology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
³ The Ph.D. Program for Translational Medicine, Taipei Medical University, Taipei, Taiwan.
⁴ Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan;; Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan.

Abstract

In this study, we observed that brown seaweed fucoidan inhibited human breast cancer progression by upregulating microRNA (miR)-29c and downregulating miR-17-5p, thereby suppressing their target genes, a disintegrin and metalloproteinase 12 (ADAM12) and phosphatase and tensin homolog (PTEN), respectively. Moreover, fucoidan reduced the luciferase activity of 3'-untranslated region reporter; treatment of cells with the miR-29c mimic or miR-17-5p inhibitor also produced similar results. These effects of fucoidan inhibited the epithelial-mesenchymal transition in breast cancer cells, as evidenced by an increase in E-cadherin and a drop in N-cadherin, and inhibited breast cancer cell survival, as evidenced by the activation of the phosphoinositide 3-kinase/Akt pathway. Taken together, these findings demonstrate that fucoidan inhibits breast cancer progression by regulating the miR-29c/ADAM12 and miR-17-5p/PTEN axes. Fucoidan is a potential chemopreventive/chemotherapeutic agent for breast cancer.

Keywords: ADAM12; Fucoidan; PTEN; breast cancer cells.; miR-17-5p; miR-29c.