Neobavaisoflavone sensitizes apoptosis via the inhibition of metastasis in TRAIL-resistant human glioma U373MG cells

Life Sci. 2014 Jan 30;95(2):101-7. doi: 10.1016/j.lfs.2013.10.035. Epub 2013 Nov 11.

Abstract

Aims: Neobavaisoflavone (NBIF), an isoflavone isolated from Psoralea corylifolia (Leguminosae), has striking anti-inflammatory and anti-cancer effects. NBIF inhibits the proliferation of prostate cancer in vitro and in vivo.

Main methods: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a key endogenous molecule that selectively induces apoptosis in cancer cells with little or no toxicity in normal cells. However, some cancer cells, including U373MG cells, are resistant to TRAIL-mediated apoptosis. We demonstrated that the cell viability, migration and invasion assay were used in U373MG glioma cells.

Key findings: In this study, we found that NBIF sensitizes human U373MG glioma cells to TRAIL-mediated apoptosis. Co-treatment of TRAIL and NBIF effectively induced Bid cleavage and activated caspases 3, 8, and 9. Importantly, DR5 expression was upregulated by NBIF. We also observed that the combination NBIF and TRAIL increased expression of BAX. We further demonstrate that NBIF induced TRAIL-mediated apoptosis in human glioma cells by suppressing migration and invasion, and by inhibiting anoikis resistance.

Significance: Taken together, our results suggest that NBIF reduces the resistance of cancer cells to TRAIL and that the combination of NBIF and TRAIL may be a new therapeutic strategy for treating TRAIL-resistant glioma cells.

Keywords: Anoikis; Apoptosis; Glioma; Metastasis; Neobavaisoflavone; TRAIL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Blotting, Western
  • Caspases / genetics
  • Caspases / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Flow Cytometry
  • Glioma / drug therapy
  • Glioma / pathology*
  • Humans
  • Isoflavones / pharmacology*
  • Neoplasm Metastasis
  • TNF-Related Apoptosis-Inducing Ligand / pharmacology*
  • Up-Regulation / drug effects

Substances

  • Antineoplastic Agents
  • Isoflavones
  • TNF-Related Apoptosis-Inducing Ligand
  • neobavaisoflavone
  • Caspases