title: Casticin suppresses self-renewal and invasion of lung cancer stem-like cells from A549 cells through down-regulation of pAkt.
abstract: A subpopulation of cancer stem cells is recognized as the cause of tumorigenesis and spreading. To investigate the effects of casticin (5,3'-dihydroxy-3,6,7,4'-tetramethoxyflavone), derived from Fructus Viticis Simplicifoliae, on lung cancer stem cells, we isolated and identified a subpopulation of lung cancer stem-like cells (LCSLCs) from non-small-cell lung carcinoma A549 cells with the features including self-renewal capacity and high invasiveness in vitro, elevated tumorigenic activity in vivo, and high expression of stemness markers CD133, CD44, and aldehyde dehydrogenase 1 (ALDH1), using serum-free suspension sphere-forming culture method. We then found that casticin could suppress the proliferation of LCSLCs in a concentration-dependent manner with an IC50 value of 0.4 μmol/L, being much stronger than that in parental A549 cells. In addition, casticin could suppress the self-renewal and invasion of LCSLCs concomitant with decreased CD133, CD44, and ALDH1 protein expression and reduced MMP-9 activity. Further experiments showed that casticin suppressed self-renewal and invasion at least partly through down-regulation of Akt phosphorylation. In conclusion, casticin suppressed the characteristics of LCSLCs, suggesting that casticin may be a candidate compound for curing lung cancer via eliminating cancer stem cells.
authors.affiliation: College of Medicine, Hunan Normal University, Changsha 410013, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Liu
authors.forename: Xiaozheng
authors.initials: X
authors.lastname: Cao
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Liu
authors.forename: Hui
authors.initials: H
authors.lastname: Guo
authors.forename: Kaiqun
authors.initials: K
authors.lastname: Ren
authors.forename: Meifang
authors.initials: M
authors.lastname: Quan
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhou
authors.forename: Honglin
authors.initials: H
authors.lastname: Xiang
authors.forename: Jianguo
authors.initials: J
authors.lastname: Cao
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D045744:Cell Line, Tumor; D015536:Down-Regulation; D005419:Flavonoids / Q000627:therapeutic use*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis*
chemical_list: D005419:Flavonoids; C054133:casticin; D051057:Proto-Oncogene Proteins c-akt
keywords: cancer stem cells; casticin; lung cancer; pAkt; therapeutic action