Tumor Biology

, Volume 37, Issue 5, pp 6673–6679 | Cite as

Zoledronic acid induces apoptosis via stimulating the expressions of ERN1, TLR2, and IRF5 genes in glioma cells

  • Cigir Biray Avci
  • Cansu Caliskan Kurt
  • Burcu Erbaykent Tepedelen
  • Ozgun Ozalp
  • Bakiye Goker
  • Zeynep Mutlu
  • Yavuz Dodurga
  • Levent Elmas
  • Cumhur Gunduz
Original Article

Abstract

Glioblastoma multiforme (GBM) is the most common and aggressive brain tumor that affects older people. Although the current therapeutic approaches for GBM include surgical resection, radiotherapy, and chemotherapeutic agent temozolomide, the median survival of patients is 14.6 months because of its aggressiveness. Zoledronic acid (ZA) is a nitrogen-containing bisphosphonate that exhibited anticancer activity in different cancers. The purpose of this study was to assess the potential effect of ZA in distinct signal transduction pathways in U87-MG cells. In this study, experiments performed on U87-MG cell line (Human glioblastoma-astrocytoma, epithelial-like cell line) which is an in vitro model of human glioblastoma cells to examine the cytotoxic and apoptotic effects of ZA. IC50 dose of ZA, 25 μM, applied on U87-MG cells during 72 h. ApoDIRECT In Situ DNA Fragmentation Assay was used to investigate apoptosis of U87MG cells. The quantitative reverse transcription polymerase chain reaction (qRT-PCR) (LightCycler480 System) was carried out for 48 gene expression like NF-κB, Toll-like receptors, cytokines, and inteferons. Our results indicated that ZA (IC50 dose) increased apoptosis 1.27-fold in U87MG cells according to control cells. According to qRT-PCR data, expression levels of the endoplasmic reticulum-nuclei-1 (ERN1), Toll-like receptor 2 (TLR2), and human IFN regulatory factor 5 (IRF5) tumor suppressor genes elevated 2.05-, 2.08-, and 2.3-fold by ZA, respectively, in U87MG cells. Our recent results indicated that ZA have a key role in GBM progression and might be considered as a potential agent in glioma treatment.

Keywords

Zoledronic acid Gene expression Glioma 

Notes

Compliance with ethical standards

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Cigir Biray Avci
    • 1
  • Cansu Caliskan Kurt
    • 1
  • Burcu Erbaykent Tepedelen
    • 2
  • Ozgun Ozalp
    • 1
  • Bakiye Goker
    • 1
  • Zeynep Mutlu
    • 1
  • Yavuz Dodurga
    • 3
  • Levent Elmas
    • 3
  • Cumhur Gunduz
    • 1
  1. 1.Medical Biology DepartmentEge University Medical SchoolIzmirTurkey
  2. 2.Department of Molecular Biology and GeneticsAvrasya University Faculty of Science and LettersTrabzonTurkey
  3. 3.Medical Biology DepartmentPamukkale University Medical SchoolDenizliTurkey

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