Bis demethoxycurcumin Suppresses Migration and Invasion of Human Cervical Cancer HeLa Cells via Inhibition of NF-ĸB, MMP-2 and -9 Pathways

Anticancer Res. 2018 Jul;38(7):3989-3997. doi: 10.21873/anticanres.12686.

Abstract

Background/aim: Bisdemethoxycurcumin (BDMC) exhibits biological activities including anticancer and anti-metastasis in human cancer cell lines, but there is no available information to show whether BDMC suppresses cell migration and invasion of human cervical cancer cells.

Materials and methods: Wound-healing, migration, invasion, zymography, and western blotting assays were used to investigate the effects of BDMC on HeLa cells in vitro.

Results: BDMC reduced the total viable cell number in a dose-dependent manner. The wound-healing assay show BDMC suppressed the movement of HeLa cells. Furthermore, the trans-well chamber assays showed that BDMC suppressed the cell migration and invasion. Gelatin zymograph assay showed that BDMC did not inhibit matrix metalloproteinase-2 (MMP-2) and -9 activities in vitro. However, western blotting assay showed that BDMC significantly reduced protein levels of growth factor receptor-bound protein 2 (GRB2), Ras homolog gene family, member A (Rho A), urokinase-type plasminogen activator (uPA), RAS, MMP-2, and N-cadherin but increased those of phosphor-extracellular-signal related kinase (p-ERK1/2), E-cadherin and nuclear factor-ĸB (NF-ĸB) in HeLa cells. Confocal laser microscopy assay was used to further confirm BDMC increased NF-ĸB when compared to controls.

Conclusion: BDMC may have potential as a novel anti-metastasis agent for the treatment of human cervical cancer.

Keywords: BDMC; Bisdemethoxycurcumin; HeLa human cervical cancer cells; NF-ĸB p65; invasion; migration.

MeSH terms

  • Blotting, Western
  • Curcumin / analogs & derivatives*
  • Curcumin / pharmacology
  • Diarylheptanoids
  • Dose-Response Relationship, Drug
  • Electrophoresis, Polyacrylamide Gel
  • Female
  • HeLa Cells
  • Humans
  • Matrix Metalloproteinase 2 / metabolism*
  • Matrix Metalloproteinase 9 / metabolism*
  • Microscopy, Confocal
  • NF-kappa B / antagonists & inhibitors*
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Uterine Cervical Neoplasms / pathology*

Substances

  • Diarylheptanoids
  • NF-kappa B
  • bisdemethoxycurcumin
  • MMP2 protein, human
  • Matrix Metalloproteinase 2
  • MMP9 protein, human
  • Matrix Metalloproteinase 9
  • Curcumin