title: Cisplatin downregulates BCL2L12, a novel apoptosis-related gene, in glioblastoma cells.
abstract: Glioblastoma progression is mainly characterized by intense apoptosis resistance and marked necrosis. Over-expression of BCL2L12, a novel member of Bcl-2 family has been shown in primary glioblastoma. BCL2L12 blocks effective caspase-3/7 maturation and inhibits p53 tumor suppressor, deriving resistance toward apoptosis and inducing extensive cell necrosis. Cisplatin is a major chemotherapeutic agent which has a broad range of anti-neoplastic activities including apoptosis induction. To investigate the effect of cisplatin on the expression of BCL2L12 in glioblastoma cells, two glioblastoma cell lines were treated with different concentrations of cisplatin for 48 h. The cell viability and IC50 was determined using MTT assay. Then, the two glioblastoma cell lines were treated with 48 h IC50 concentration of cisplatin for 24, 48, and 72 h. Apoptosis induction was analyzed by fluorescence microscopy and flow cytometry. Gene expression study was performed on BCL2L12 and TBP as target and internal control genes, respectively. The quantitative real-time polymerase chain reaction results showed that BCL2L12 gene expression was significantly (p = 0.001) downregulated in the presence of cisplatin. In conclusion, cisplatin treatment induced a time-dependent apoptosis in glioblastoma cells, at least partially via downregulation of BCL2L12 gene expression.
authors.affiliation: Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran. ms.taghavi@srbiau.ac.ir
authors.forename: Mahdieh Sadat
authors.initials: MS
authors.lastname: Taghavi
authors.forename: Azim
authors.initials: A
authors.lastname: Akbarzadeh
authors.forename: Reza
authors.initials: R
authors.lastname: Mahdian
authors.forename: Kayhan
authors.initials: K
authors.lastname: Azadmanesh
authors.forename: Gholamreza
authors.initials: G
authors.lastname: Javadi
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002945:Cisplatin / Q000008:administration & dosage*; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005909:Glioblastoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D006801:Humans; D009124:Muscle Proteins / Q000096:biosynthesis* / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: C430100:BCL2L12 protein, human; D009124:Muscle Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D053148:Caspase 3; D002945:Cisplatin