title: MLN4924 and 2DG combined treatment enhances the efficiency of radiotherapy in breast cancer cells.
abstract: Two-deoxy-D-glucose (2DG) causes cytotoxicity in the cancer cells by disrupting the thiol metabolism, and MLN4924 inactivates the SCF E3 ligase and so causes the accumulation of its substrates which trigger apoptosis and hence might enhance the efficiency of radiotherapy and overcame on the radioresistance of the cancer cells.
  
  
  
  SKBR3 and MCF-7 breast cancer cells were treated with 500 μM 2DG and/or MLN4924 (30, 100, 200 and 300 nM), and in combination in the presence and absence of 1, 1.5 and 2 Gy gamma irradiation. The effects of the treatments - 2DG, MLN4924, irradiation alone and combined - on MCF-7 and SKBR3 cell lines were evaluated by MTT assay, TUNEL assay, cell death detection, Q-PCR for caspase-3 and Bcl-2 expression analysis, and finally clonogenic survival assay.
  
  
  
  The treatments enhanced the further radio cytotoxicity via inducing the apoptosis cell signaling gene, caspase-3. The 2DG and MLN4924 treatments could act as a radiosensitizer, especially on the SKBR3 cells, and further sensitized the cells with a sensitivity enhancement ratio (SER) of 1.41 and 1.27 in SKBR3 and MCF-7 cells, respectively.
  
  
  
  The combined chemo-radiotherapy might improve the breast cancer treatment outcome.
authors.affiliation: a Immunology Research Center, Tabriz University of Medical Sciences , Tabriz , Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Oladghaffari
authors.affiliation: b Medical Physics Department , Cellular & Molecular Biology Research Center, Babol University of Medical Sciences , Babol , Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Shabestani Monfared
authors.affiliation: c Department of Medical Physics, Faculty of Medicine , Tabriz University of Medical Sciences , Tabriz , Iran.
authors.forename: Alireza
authors.initials: A
authors.lastname: Farajollahi
authors.affiliation: a Immunology Research Center, Tabriz University of Medical Sciences , Tabriz , Iran.
authors.forename: Behzad
authors.initials: B
authors.lastname: Baradaran
authors.affiliation: d Shahid Beheshti University of Medical Sciences , Tehran , Iran.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Mohammadi
authors.affiliation: a Immunology Research Center, Tabriz University of Medical Sciences , Tabriz , Iran.
authors.forename: Dariush
authors.initials: D
authors.lastname: Shanehbandi
authors.affiliation: e Department of Biostatistics and Epidemiology, Faculty of Health , Medical Education Research Center, Tabriz University of Medical Sciences , Tabriz , Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Asghari Jafar Abadi
authors.affiliation: a Immunology Research Center, Tabriz University of Medical Sciences , Tabriz , Iran.|c Department of Medical Physics, Faculty of Medicine , Tabriz University of Medical Sciences , Tabriz , Iran.
authors.forename: Jalil
authors.initials: J
authors.lastname: Pirayesh Islamian
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000473:pathology / Q000628:therapy*; D059248:Chemoradiotherapy / Q000379:methods*; D003517:Cyclopentanes / Q000008:administration & dosage*; D003847:Deoxyglucose / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D061986:MCF-7 Cells; D011743:Pyrimidines / Q000008:administration & dosage*; D011879:Radiotherapy Dosage; D016896:Treatment Outcome
chemical_list: D003517:Cyclopentanes; D011743:Pyrimidines; D003847:Deoxyglucose; C539933:pevonedistat
keywords: 2-deoxy-D-glucose; MLN4924; breast cancer; caspase-3; combination therapy; radiosensitizer