Title: Sulforaphane inhibits cancer stem-like cell properties and cisplatin resistance through miR-214-mediated downregulation of c-MYC in non-small cell lung cancer
Abstract: // Qian-Qian Li 1, * , You-Ke Xie 1, * , Yue Wu 1 , Lin-Lin Li 1 , Ying Liu 1 , Xiao-Bo Miao 1 , Qiu-Zhen Liu 1 , Kai-Tai Yao 1 , Guang-Hui Xiao 1 1 Cancer Institute, Southern Medical University, Guangzhou 510515, China * These authors have contributed equally to this work Correspondence to: Guang-Hui Xiao, email: [email protected] Keywords: sulforaphane, c-MYC, miR-214, cisplatin, lung cancer Received: June 11, 2016 Accepted: December 27, 2016 Published: January 05, 2017 ABSTRACT We herein report that sulforaphane (SFN), a potent anti-cancer and well-tolerated dietary compound, inhibits cancer stem-like cell (CSC) properties and enhances therapeutic efficacy of cisplatin in human non-small cell lung cancer (NSCLC). SFN exerted these functions through upregulation of miR-214, which in turn targets the coding region of c-MYC . This finding was further corroborated by our observations that plasmid or lentiviral vector-mediated expression of 3'UTR-less c-MYC cDNA and cisplatin- or doxorubicin-induced endogenous c-MYC accumulation was similarly suppressed by either SFN or miR-214. Further, we showed that the reported inhibitory effects of SFN on β-catenin are also mediated by miR-214. SFN/miR-214 signaling inhibited CSC properties and enhanced the cytotoxicity of chemotherapeutic drugs in vitro . Experiments with nude mice carrying xenograft tumors showed that SFN sensitized NSCLC cells to cisplatin's efficacy, which is accompanied by inhibition of cisplatin-induced c-MYC accumulation in tumor tissues. Our results provided strong evidence and mechanisms to support consideration of SFN or synthetic derivatives as a therapeutic agent in combination with cisplatin for the treatment of patients with NSCLC and, potentially, other types of c-MYC-addicted tumors.