title: Glabridin inhibits cancer stem cell-like properties of human breast cancer cells: An epigenetic regulation of miR-148a/SMAd2 signaling.
abstract: In breast cancer, the cancer stem cells (CSCs) are thought to be the main cause of metastasis and recurrence. Targeting of CSCs or cancer cells with stem cell-like properties has become a new approach for the treatment of breast cancer. Glabridin (GLA), a phytochemical from the root of Glycyrrhiza glabra, exhibited effective antitumor properties in various human cancer cells. However, the roles of GLA in the regulation of CSC-like properties and the underlying molecular mechanisms remain unclear. Here, we reported that GLA attenuated the CSC-like properties through microRNA-148a (miR-148a)/transforming growth factor beta (TGFβ)-SMAD2 signal pathway in vitro and in vivo. In MDA-MB-231 and Hs-578T breast cancer cell lines, GLA enhanced the expression of miR-148a through DNA demethylation. By targeting of the SMAD2-3'-UTR, miR-148a blocked the expression/activation of SMAD2, and in turn, restored the epithelial characteristics, adhesive abilities, and CSC-like properties. Furthermore, in mouse xenograft models, we also confirmed that GLA attenuated the tumor growth, mesenchymal characteristics, and CSCs-like properties via demethylation-activated miR-148a. Our findings suggested a potential treatment strategy to reduce the CSCs-like properties, and therefore enhance the effectiveness of breast cancer therapy.
authors.affiliation: Department of Nutrition and Food Hygiene, The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Fei
authors.initials: F
authors.lastname: Jiang
authors.affiliation: Department of Nutrition and Food Hygiene, The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Nutrition and Food Hygiene, The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Juan
authors.initials: J
authors.lastname: Mu
authors.affiliation: Department of Nutrition and Food Hygiene, The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Hu
authors.affiliation: Department of Nutrition and Food Hygiene, The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Department of Nutrition and Food Hygiene, The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Xingxing
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Nutrition and Food Hygiene, The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Lu
authors.initials: L
authors.lastname: Si
authors.forename: Shilong
authors.initials: S
authors.lastname: Ning
authors.affiliation: Department of Nutrition and Food Hygiene, The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Li
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D019175:DNA Methylation / Q000187:drug effects; D044127:Epigenesis, Genetic / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007529:Isoflavones / Q000008:administration & dosage* / Q000494:pharmacology; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism; D010636:Phenols / Q000008:administration & dosage* / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D051899:Smad2 Protein / Q000235:genetics* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D007529:Isoflavones; C550570:MIRN148 microRNA, human; D035683:MicroRNAs; D010636:Phenols; C497782:SMAD2 protein, human; D051899:Smad2 Protein; C107601:glabridin
keywords: cancer stem cell-like properties; epigenetic regulation; glabridin; microRNA-148a; transforming growth factor beta-SMADs signal pathway