title: The synthetic flavonoid WYC02-9 inhibits colorectal cancer cell growth through ROS-mediated activation of MAPK14 pathway.
abstract: OBJECTIVE
  Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide. In this study, we explored the anti-cancer activity of WYC02-9, a synthetic protoapigenone, on human HCT116 CRC cells.
  
  
  METHODS
  The anti-cancer activity of WYC02-9 and its underlying mechanisms were analyzed using XTT cell proliferation assays, colony formation assays, FACS analysis, annexin V staining, immunoblotting analysis, reactive oxygen species (ROS) generation assays, soft agar assays, a nude mice xenograft study and immunohistochemistry assays.
  
  
  RESULTS
  Data showed that WYC02-9 suppressed CRC cell growth by arresting cells at G2/M and inducing cell death via apoptotic pathways. Further analysis demonstrated that WYC02-9-induced apoptosis was mediated by the activation of a ROS-mediated MAPK14 pathway. An in vivo xenograft study revealed that WYC02-9 enhanced MAP2K3/6 and MAPK14 phosphorylation, induced apoptosis, and suppressed CRC tumor growth.
  
  
  CONCLUSIONS
  WYC02-9 exerts its anti-tumor effect via ROS/MAPK14-induced apoptosis and has the potential to be developed as a chemotherapeutic agent for CRC.
authors.affiliation: Department of Biological Science and Technology, I-Shou University, Kaohsiung, Taiwan.
authors.forename: Yun-Ju
authors.initials: YJ
authors.lastname: Chen
authors.forename: Hsin-Pao
authors.initials: HP
authors.lastname: Chen
authors.forename: Yu-Jen
authors.initials: YJ
authors.lastname: Cheng
authors.forename: Yu-Heng
authors.initials: YH
authors.lastname: Lin
authors.forename: Kuang-Wen
authors.initials: KW
authors.lastname: Liu
authors.forename: Yun-Ju
authors.initials: YJ
authors.lastname: Chen
authors.forename: Ming-Feng
authors.initials: MF
authors.lastname: Hou
authors.forename: Yang-Chang
authors.initials: YC
authors.lastname: Wu
authors.forename: Yi-Chen
authors.initials: YC
authors.lastname: Lee
authors.forename: Shyng-Shiou
authors.initials: SS
authors.lastname: Yuan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D003512:Cyclohexanones / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D005260:Female; D047309:Flavones / Q000494:pharmacology*; D055785:Gene Knockdown Techniques; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D048308:Mitogen-Activated Protein Kinase 14 / Q000378:metabolism*; D009368:Neoplasm Transplantation; D010936:Plant Extracts / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014183:Transplantation, Heterologous; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D003512:Cyclohexanones; D047309:Flavones; D010936:Plant Extracts; D017382:Reactive Oxygen Species; C524112:protoapigenone; D048308:Mitogen-Activated Protein Kinase 14