title: Zoledronic acid induces apoptosis via stimulating the expressions of ERN1, TLR2, and IRF5 genes in glioma cells.
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.
authors.affiliation: Medical Biology Department, Ege University Medical School, Bornova, Izmir, Turkey. cbavci@gmail.com.
authors.forename: Cigir
authors.initials: C
authors.lastname: Biray Avci
authors.affiliation: Medical Biology Department, Ege University Medical School, Bornova, Izmir, Turkey.
authors.forename: Cansu Caliskan
authors.initials: CC
authors.lastname: Kurt
authors.affiliation: Department of Molecular Biology and Genetics, Avrasya University Faculty of Science and Letters, Trabzon, Turkey.
authors.forename: Burcu Erbaykent
authors.initials: BE
authors.lastname: Tepedelen
authors.affiliation: Medical Biology Department, Ege University Medical School, Bornova, Izmir, Turkey.
authors.forename: Ozgun
authors.initials: O
authors.lastname: Ozalp
authors.affiliation: Medical Biology Department, Ege University Medical School, Bornova, Izmir, Turkey.
authors.forename: Bakiye
authors.initials: B
authors.lastname: Goker
authors.affiliation: Medical Biology Department, Ege University Medical School, Bornova, Izmir, Turkey.
authors.forename: Zeynep
authors.initials: Z
authors.lastname: Mutlu
authors.affiliation: Medical Biology Department, Pamukkale University Medical School, Denizli, Turkey.
authors.forename: Yavuz
authors.initials: Y
authors.lastname: Dodurga
authors.affiliation: Medical Biology Department, Pamukkale University Medical School, Denizli, Turkey.
authors.forename: Levent
authors.initials: L
authors.lastname: Elmas
authors.affiliation: Medical Biology Department, Ege University Medical School, Bornova, Izmir, Turkey.
authors.forename: Cumhur
authors.initials: C
authors.lastname: Gunduz
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D053938:DNA Fragmentation; D004164:Diphosphonates / Q000494:pharmacology*; D004722:Endoribonucleases / Q000235:genetics*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D005910:Glioma / Q000235:genetics*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D050835:Interferon Regulatory Factors / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D051195:Toll-Like Receptor 2 / Q000235:genetics; D000077211:Zoledronic Acid
chemical_list: D000970:Antineoplastic Agents; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; C431713:IRF5 protein, human; D007093:Imidazoles; D050835:Interferon Regulatory Factors; D051195:Toll-Like Receptor 2; D000077211:Zoledronic Acid; C528229:ERN1 protein, human; D017346:Protein Serine-Threonine Kinases; D004722:Endoribonucleases
keywords: Gene expression; Glioma; Zoledronic acid