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

Research Paper

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 Wu1,2,3,4, Ming-De Yan5, Alexander T.H. Wu6, Kevin Sheng-Po Yuan7, Shing Hwa Liu1,8 ✉

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

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Citation:
Wu SY, Yan MD, Wu ATH, Yuan KSP, Liu SH. 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; 7(15):2408-2419. doi:10.7150/jca.15703. Available from http://www.jcancer.org/v07p2408.htm

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