title: The synthetic flavonoid WYC02-9 inhibits cervical cancer cell migration/invasion and angiogenesis via MAPK14 signaling.
abstract: OBJECTIVE
  Development of flavonoids as potential chemotherapeutic agents for cervical cancer may open new avenues in anticancer drug design. In this study, the cytotoxic activity and anti-migration/invasion/angiogenesis efficiency of the synthetic flavonoid WYC02-9 on cervical cancer and the underlying mechanisms are explored.
  
  
  METHODS
  XTT cell viability assay, apoptosis assays, cell cycle analysis, and immunoblotting analysis were applied to study the biologic activity of WYC02-9. Anchorage independent soft agar assay and xenograft nude mouse model were applied to study the anti-tumor effect of WYC02-9 in vivo. Wound healing assay, transwell invasion assay, and gelatin zymography analysis were applied to study the effect of WYC02-9 on cancer cell migration and invasion. Tube formation analysis, zebrafish angiogenesis model, and nude mice Matrigel plug angiogenesis assay were applied to study the effect of WYC02-9 on angiogenesis.
  
  
  RESULTS
  WYC02-9 induced cytotoxicity on cervical cancer cells by promoting apoptosis and G2/M cell cycle arrest. WYC02-9 inhibited cervical cancer cell migration/invasion and angiogenesis in vitro and in vivo via MAPK14 pathway.
  
  
  CONCLUSIONS
  WYC02-9 significantly inhibited cervical cancer cell proliferation/migration/invasion and angiogenesis in vitro and in vivo. WYC02-9 may be a promising drug candidate for cervical cancer chemotherapy.
authors.affiliation: Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Translational Research Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Yun-Ju
authors.initials: YJ
authors.lastname: Chen
authors.forename: Yu-Jen
authors.initials: YJ
authors.lastname: Cheng
authors.forename: Amos C
authors.initials: AC
authors.lastname: Hung
authors.forename: Yang-Chang
authors.initials: YC
authors.lastname: Wu
authors.forename: Ming-Feng
authors.initials: MF
authors.lastname: Hou
authors.forename: Yu-Chang
authors.initials: YC
authors.lastname: Tyan
authors.forename: Shyng-Shiou F
authors.initials: SS
authors.lastname: Yuan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D003512:Cyclohexanones / Q000494:pharmacology*; D005260:Female; D047309:Flavones / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051379:Mice; D008819:Mice, Nude; D048308:Mitogen-Activated Protein Kinase 14 / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D002583:Uterine Cervical Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D023041:Xenograft Model Antitumor Assays; D015027:Zebrafish
chemical_list: D003512:Cyclohexanones; D047309:Flavones; D005419:Flavonoids; C585836:WYC02-9; D048308:Mitogen-Activated Protein Kinase 14
keywords: Angiogenesis; Cervical cancer; Invasion; Migration; Viability; WYC02-9