Tetrandrine inhibits human brain glioblastoma multiforme GBM 8401 cancer cell migration and invasion in vitro

Environ Toxicol. 2019 Apr;34(4):364-374. doi: 10.1002/tox.22691. Epub 2018 Dec 13.

Abstract

Tetrandrine (TET) has been reported to induce anti-cancer activity in many human cancer cells and also to inhibit cancer cell migration and invasion. However, there are no reports to show TET inhibits cell migration and invasion in human brain glioblastoma multiforme GBM 8401 cells. In this study, we investigated the anti-metastasis effects of TET on GBM 8401 cells in vitro. Under sub-lethal concentrations (from 1, 5 up to 10 μM), TET significantly inhibited cell mobility, migration and invasion of GBM 8401 cells that were assayed by wound healing and Transwell assays. Gelatin zymography assay showed that TET inhibited MMP-2 activity in GBM 8401 cells. Western blotting results indicated that TET inhibited several key metastasis-related proteins, such as p-EGFR(Tyr1068) , SOS-1, GRB2, Ras, p-AKT(Ser473) and p-AKT(Thr308) , NF-κB-p65, Snail, E-cadherin, N-cadherin, NF-κB, MMP-2 and MMP-9 that were significant reduction at 24 and 48 hours treatment by TET. TET reduced MAPK signaling associated proteins such as p-JNK1/2 and p-c-Jun in GBM 8401 cells. The electrophoretic mobility shift (EMSA) assay was used to investigate NF-κB and DNA binding was reduced by TET in a dose-dependently. Based on these findings, we suggested that TET could be used in anti-metastasis of human brain glioblastoma multiforme GBM 8401 cells in the future.

Keywords: GBM 8401 cells; MMP-2; NF-κB; Tetrandrine (TET); migration and invasion.

MeSH terms

  • Anticarcinogenic Agents / pharmacology*
  • Benzylisoquinolines / pharmacology*
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Glioblastoma / metabolism
  • Glioblastoma / pathology*
  • Humans
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • NF-kappa B / metabolism
  • Neoplasm Invasiveness
  • Signal Transduction

Substances

  • Anticarcinogenic Agents
  • Benzylisoquinolines
  • NF-kappa B
  • tetrandrine
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9