Sulforaphane inhibits thyroid cancer cell growth and invasiveness through the reactive oxygen species-dependent pathway

// Liping Wang 1, 2, * , Zhufang Tian 2, * , Qi Yang 1 , Heng Li 2 , Haixia Guan 3 , Bingyin Shi 1 , Peng Hou 1 , Meiju Ji 4 1 Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University School of Medicine, Xi'an 710061, P.R. China 2 Department of Endocrinology, Xi'an Central Hospital, Xi'an 710003, P.R. China 3 Department of Endocrinology and Metabolism, The First Affiliated Hospital of China Medical University, Shenyang 110001, P.R. China 4 Center 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 Correspondence to: Peng Hou, e-mail: phou@mail.xjtu.edu.cn Meiju Ji, e-mail: mjji0409@163.com Keywords: thyroid cancer, sulforaphane (SFN), reactive oxygen species (ROS), signaling pathways Received: March 12, 2015 Accepted: July 06, 2015 Published: July 17, 2015 ABSTRACT 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.