Sulforaphane inhibits thyroid cancer cell growth and invasiveness through the reactive oxygen species-dependent pathway
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Liping Wang1,2,*, Zhufang Tian2,*, Qi Yang1, Heng Li2, Haixia Guan3, Bingyin Shi1, Peng Hou1, Meiju Ji4
1Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University School of Medicine, Xi'an 710061, P.R. China
2Department of Endocrinology, Xi'an Central Hospital, Xi'an 710003, P.R. China
3Department of Endocrinology and Metabolism, The First Affiliated Hospital of China Medical University, Shenyang 110001, P.R. China
4Center for Translational Medicine, The First Affiliated Hospital of Xi'an Jiaotong University School of Medicine, Xi'an 710061, P.R. China
*These authors have contributed equally to this work
Peng Hou, e-mail: [email protected]
Meiju Ji, e-mail: [email protected]
Keywords: thyroid cancer, sulforaphane (SFN), reactive oxygen species (ROS), signaling pathways
Received: March 12, 2015 Accepted: July 06, 2015 Published: July 17, 2015
Sulforaphane (SFN), a natural compound derived from broccoli/broccoli sprouts, has been demonstrated to be used as an antitumor agent in different types of cancers. However, its antitumor effect in thyroid cancer remains largely unknown. The aim of the study was to investigate the therapeutic potential of SFN for thyroid cancer and explore the mechanisms underlying antitumor effects of SFN by in vitro and in vivo studies. Our data demonstrated that SFN significantly inhibited thyroid cancer cell proliferation in a dose- and time-dependent manner, induced G2/M phase cell cycle arrest and apoptosis, and inhibited thyroid cancer cell migration and invasion by suppressing epithelial-mesenchymal transition (EMT) process and expression of Slug, Twist, MMP-2 and -9. Mechanically, SFN inhibited thyroid cancer cell growth and invasiveness through repressing phosphorylation of Akt, enhancing p21 expression by the activation of Erk and p38 signaling cascades, and promoting mitochondrial-mediated apoptosis via reactive oxygen species (ROS)-dependent pathway. Growth of xenograft tumors derived from thyroid cancer cell line FTC133 in nude mice was also significantly inhibited by SFN. Importantly, we did not find significant effect of SFN on body weight and liver function of mice. Collectively, we for the first time demonstrate that SFN is a potentially effective antitumor agent for thyroid cancer.
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