Sulforaphane inhibits cancer stem-like cell properties and cisplatin resistance through miR-214-mediated downregulation of c-MYC in non-small cell lung cancer
| Autor: | Qiuzhen Liu, Qian-Qian Li, Linlin Li, Guang-Hui Xiao, Ying Liu, Yue Wu, You-Ke Xie, Xiao-Bo Miao, Kaitai Yao |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Lung Neoplasms Cell sulforaphane cisplatin Pharmacology miR-214 chemistry.chemical_compound 0302 clinical medicine Isothiocyanates Carcinoma Non-Small-Cell Lung Cytotoxicity 3' Untranslated Regions beta Catenin Mice Inbred BALB C Reverse Transcriptase Polymerase Chain Reaction Gene Expression Regulation Neoplastic medicine.anatomical_structure c-MYC Oncology 030220 oncology & carcinogenesis Sulfoxides Neoplastic Stem Cells medicine.drug Research Paper Cell Survival Blotting Western Down-Regulation Mice Nude Antineoplastic Agents Cell Line Proto-Oncogene Proteins c-myc 03 medical and health sciences Downregulation and upregulation Cell Line Tumor medicine Animals Humans Lung cancer Cisplatin business.industry Cancer medicine.disease Xenograft Model Antitumor Assays MicroRNAs lung cancer 030104 developmental biology chemistry A549 Cells Doxorubicin Drug Resistance Neoplasm business Sulforaphane |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | // 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: ghxiaohh@hotmail.com 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. |
| Databáze: | OpenAIRE |
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