In Vitro Effects of Mesenchymal Stem Cells and Various Agents on Apoptosis of Glioblastoma Cells

Turk Neurosurg. 2019;29(1):26-32. doi: 10.5137/1019-5149.JTN.21827-17.2.

Abstract

Aim: To investigate a new anti-tumor treatment method using stem cells transfected with specific genes and proteins that induce apoptosis in tumor cells.

Material and methods: We used glioblastoma (GBM) cells and human adipose tissue-derived mesenchymal stem cells (ADMSCs) in this study. The AD-MSCs were transfected with the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). To overcome apoptosis resistance in tumor cells, we used suberoylanilide hydroxamic acid (SAHA) as the histone deacetylase inhibitor and embelin as the X-linked inhibitor of apoptosis protein (XIAP). In addition, we silenced the XIAP gene on GBM cells with the shXIAP plasmid. Following the determination of half-maximal effective concentration (EC50%) doses of SAHA and embelin, GBM cells were incubated with them for 24 hours. XIAP-silenced and XIAP-non-silenced GBM cells were cultured with TRAIL-nontransfected and TRAIL-transfected stem cells for 24 hours. Viability and cell cycle analysis of all groups were determined using annexin V/propidium iodide and cell cycle method via flow cytometry.

Results: TRAIL-transfected AD-MSCs, XIAP silencing, embelin, and SAHA induced apoptosis in GBM cells and decreased their proliferation, whereas TRAIL-non-tranfected AD-MSCs did not.

Conclusion: Engineered stem cell therapies and molecular studies show promise in developing combination therapies for effective treatment of GBM.

MeSH terms

  • Adult
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Benzoquinones / pharmacology
  • Cell Line, Tumor
  • Gene Silencing
  • Glioblastoma / pathology*
  • Histone Deacetylase Inhibitors / pharmacology
  • Humans
  • Mesenchymal Stem Cells*
  • TNF-Related Apoptosis-Inducing Ligand / metabolism
  • Vorinostat / pharmacology
  • X-Linked Inhibitor of Apoptosis Protein / antagonists & inhibitors*

Substances

  • Antineoplastic Agents
  • Benzoquinones
  • Histone Deacetylase Inhibitors
  • TNF-Related Apoptosis-Inducing Ligand
  • X-Linked Inhibitor of Apoptosis Protein
  • XIAP protein, human
  • Vorinostat
  • embelin