title: Physcion inhibits the metastatic potential of human colorectal cancer SW620 cells in vitro by suppressing the transcription factor SOX2.
abstract: OBJECTIVE
  Physcion, an anthraquinone derivative, exhibits hepatoprotective, anti-inflammatory, anti-microbial and anti-cancer activities. In this study we examined whether and how physcion inhibited metastatic potential of human colorectal cancer cells in vitro.
  
  
  METHODS
  Human colorectal cancer cell line SW620 was tested. Cell migration and invasion were assessed using a wound healing and Transwell assay, respectively. The expression levels of transcription factor SOX2 in the cells were modulated with shRNA targeting SOX2 and SOX2 overexpressing plasmid. The expression of target molecules involved in epithelial-mesenchymal transition (EMT) process and the signaling pathways was determined with Western blots or qRT-PCR. ROS levels were measured using DCF-DA.
  
  
  RESULTS
  Physcion (2.5, 5 mol/L) did not affect the cell viability, but dose-dependently inhibited the cell adhesion, migration and invasion. Physcion also inhibited the EMT process in the cells, as evidenced by the increased epithelial marker E-cadherin expression, and by decreased expression of mesenchymal markers N-cadherin, vimentin, fibronectin and α-SMA, as well as transcriptional repressors Snail, Slug and Twist. Physcion suppressed the expression of SOX2, whereas overexpression of SOX2 abrogated the inhibition of physcion on metastatic behaviors. Physcion markedly increased ROS production and phosphorylation of AMPK and GSK3β in the cells, whereas the AMPK inhibitor compound C or the ROS inhibitor NAC abolished the inhibition of physcion on metastatic behaviors.
  
  
  CONCLUSIONS
  Physcion inhibits the metastatic potential of human colorectal cancer cells in vitro via activating ROS/AMPK/GSK3β signaling pathways and suppressing SOX2.
authors.affiliation: Medical College of Qingdao University, Qingdao 266071, China.
authors.forename: Yan-tao
authors.initials: YT
authors.lastname: Han
authors.affiliation: Medical College of Qingdao University, Qingdao 266071, China.
authors.forename: Xue-hong
authors.initials: XH
authors.lastname: Chen
authors.affiliation: Medical College of Qingdao University, Qingdao 266071, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Gao
authors.affiliation: Medical College of Qingdao University, Qingdao 266071, China.
authors.forename: Jun-li
authors.initials: JL
authors.lastname: Ye
authors.affiliation: Medical College of Qingdao University, Qingdao 266071, China.
authors.forename: Chun-bo
authors.initials: CB
authors.lastname: Wang
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015536:Down-Regulation / Q000187:drug effects*; D004642:Emodin / Q000031:analogs & derivatives* / Q000494:pharmacology; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism; D006801:Humans; D009362:Neoplasm Metastasis / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012007:Rectum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D055748:SOXB1 Transcription Factors / Q000235:genetics*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D000071679:Glycogen Synthase Kinase 3 beta; D055372:AMP-Activated Protein Kinases; C008905:physcione; D004642:Emodin