title: 8-bromo-5-hydroxy-7-methoxychrysin targeting for inhibition of the properties of liver cancer stem cells by modulation of Twist signaling.
abstract: Emerging evidence has suggested that cancer stem cells with expression of surface biomarkers including CD133 and CD44 have more aggressive biological behavior, including epithelial-mesenchymal transition (EMT), which are closely related to invasion. The upregulation and nuclear relocation of the EMT regulator Twist1 have been implicated in the tumor invasion and metastasis of human hepatocellular carcinoma (HCC). In this study, we aimed to isolate and characterize a small population of CD133+ cells that existed in the HCC cell line SMMC-7721 by MACS and investigated the possible roles of 8-bromo-7-methoxychrysin (BrMC), a synthetic analogue of chrysin, in inhibiting the properties of CD133+ sphere-forming cells (SFCs) derived from the HCC cell line SMMC-7721, namely liver cancer stem cells (LCSCs). Based on the data, BrMC inhibited the proliferation, self-renewal and invasion of LCSCs in vitro and in vivo, downregulated the expression of the LCSC biomarkers CD133 and CD44 and induced EMT by downregulating the expression of Twist and β-catenin in LCSCs. BrMC potentiated the inhibition of LCSCs self-renewal after reduction of twist protein levels, which was attenuated when twist was overexpressed. This study not only provides an important experimental and theoretical basis for investigation of BrMC in LCSCs, but also helps in the development of effective therapeutic medicine for HCC.
authors: Medical College, Hunan Normal University, Changsha, Hunan 410013, P.R. China.
authors: Kai-Qun
authors: KQ
authors: Ren
authors: Xiao-Zheng
authors: XZ
authors: Cao
authors: Zhi-Hong
authors: ZH
authors: Liu
authors: Hui
authors: H
authors: Guo
authors: Mei-Fang
authors: MF
authors: Quan
authors: Fei
authors: F
authors: Liu
authors: Ling
authors: L
authors: Jiang
authors: Hong-Lin
authors: HL
authors: Xiang
authors: Xi-Yun
authors: XY
authors: Deng
authors: Jian-Guo
authors: JG
authors: Cao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects*; D051879:Twist-Related Protein 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: C552860:8-bromo-7-methoxychrysin; D005419:Flavonoids; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1