Turkish Neurosurgery 2019 , Vol 29 , Num 1
In Vitro Effects of Mesenchymal Stem Cells and Various Agents on Apoptosis of Glioblastoma Cells
Bahattin TANRIKULU1,Ibrahim ZIYAL2,Yasar BAYRI2
1Acıbadem Mehmet Ali Aydınlar University, School of Medicine, Department of Neurosurgery, Division of Pediatric Neurosurgery, Istanbul, Turkey
2Marmara University, School of Medicine, Department of Neurosurgery, Istanbul, Turkey
DOI : 10.5137/1019-5149.JTN.21827-17.2 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. Keywords : Embelin, Glioblastoma, Mesenchymal stem cell, SAHA, TRAIL

Corresponding author : Bahattin TANRIKULU, bahattintanrikulu@gmail.com