The synthetic flavonoid WYC02-9 inhibits cervical cancer cell migration/invasion and angiogenesis via MAPK14 signaling

Gynecol Oncol. 2013 Dec;131(3):734-43. doi: 10.1016/j.ygyno.2013.10.012. Epub 2013 Oct 18.

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.

Conclusion: 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.

Keywords: Angiogenesis; Cervical cancer; Invasion; Migration; Viability; WYC02-9.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cell Cycle Checkpoints / drug effects
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Cyclohexanones / pharmacology*
  • Female
  • Flavones / pharmacology*
  • Flavonoids / pharmacology
  • HeLa Cells
  • Humans
  • MAP Kinase Signaling System / drug effects*
  • Mice
  • Mice, Nude
  • Mitogen-Activated Protein Kinase 14 / metabolism*
  • Neovascularization, Pathologic / drug therapy
  • Neovascularization, Pathologic / enzymology
  • Neovascularization, Pathologic / pathology
  • Uterine Cervical Neoplasms / blood supply
  • Uterine Cervical Neoplasms / drug therapy*
  • Uterine Cervical Neoplasms / enzymology
  • Uterine Cervical Neoplasms / pathology
  • Xenograft Model Antitumor Assays
  • Zebrafish

Substances

  • Cyclohexanones
  • Flavones
  • Flavonoids
  • WYC02-9
  • Mitogen-Activated Protein Kinase 14