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: 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.
authors.affiliation: Cancer Institute, Southern Medical University, Guangzhou 510515, China.
authors.forename: Qian-Qian
authors.initials: QQ
authors.lastname: Li
authors.affiliation: Cancer Institute, Southern Medical University, Guangzhou 510515, China.
authors.forename: You-Ke
authors.initials: YK
authors.lastname: Xie
authors.affiliation: Cancer Institute, Southern Medical University, Guangzhou 510515, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Cancer Institute, Southern Medical University, Guangzhou 510515, China.
authors.forename: Lin-Lin
authors.initials: LL
authors.lastname: Li
authors.affiliation: Cancer Institute, Southern Medical University, Guangzhou 510515, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Cancer Institute, Southern Medical University, Guangzhou 510515, China.
authors.forename: Xiao-Bo
authors.initials: XB
authors.lastname: Miao
authors.affiliation: Cancer Institute, Southern Medical University, Guangzhou 510515, China.
authors.forename: Qiu-Zhen
authors.initials: QZ
authors.lastname: Liu
authors.affiliation: Cancer Institute, Southern Medical University, Guangzhou 510515, China.
authors.forename: Kai-Tai
authors.initials: KT
authors.lastname: Yao
authors.affiliation: Cancer Institute, Southern Medical University, Guangzhou 510515, China.
authors.forename: Guang-Hui
authors.initials: GH
authors.lastname: Xiao
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000072283:A549 Cells; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002945:Cisplatin / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D017879:Isothiocyanates / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013454:Sulfoxides; D023041:Xenograft Model Antitumor Assays; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D000970:Antineoplastic Agents; D017879:Isothiocyanates; C547397:MIRN214 microRNA, human; C489427:MYC protein, human; D035683:MicroRNAs; D016271:Proto-Oncogene Proteins c-myc; D013454:Sulfoxides; D051176:beta Catenin; D004317:Doxorubicin; C016766:sulforaphane; D002945:Cisplatin
keywords: c-MYC; cisplatin; lung cancer; miR-214; sulforaphane