Sulforaphane inhibits cancer stem-like cell properties and cisplatin resistance through miR-214-mediated downregulation of c-MYC in non-small cell lung cancer
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Qian-Qian Li1,*, You-Ke Xie1,*, Yue Wu1, Lin-Lin Li1, Ying Liu1, Xiao-Bo Miao1, Qiu-Zhen Liu1, Kai-Tai Yao1, Guang-Hui Xiao1
1Cancer Institute, Southern Medical University, Guangzhou 510515, China
*These authors have contributed equally to this work
Guang-Hui Xiao, email: firstname.lastname@example.org
Keywords: sulforaphane, c-MYC, miR-214, cisplatin, lung cancer
Received: June 11, 2016 Accepted: December 27, 2016 Published: January 05, 2017
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.
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