title: TNF-α exerts higher cytotoxic effect on MCF-7 multidrug resistant derivative, role of Akt activation.
abstract: BACKGROUND
  TNF-α is a pleiotropic cytokine which activates different downstream signaling pathways leading cells to death or survival. In some in vitro examinations, TNF-α treatment demonstrated higher cytotoxic effects on MDR cancer cell lines compared to their parental counterparts.
  
  
  OBJECTIVE
  This study investigated effects of TNF-α in MCF-7 and its mitoxantrone (MX) resistant variant of breast cancer cell line, MCF-7/MX. Moreover, the role of Akt phosphorylation in TNF-α effect was also investigated.
  
  
  METHODS
  Akt phosphorylation was evaluated using Western blotting and TNF-α effect was examined using cytotoxicity assay following treatment of the cells with TNF-α .
  
  
  RESULTS
  TNF-α treatment exerted higher cytotoxic effects on MCF-7/MX compared to MCF-7 cells. Akt phosphorylation was enhanced following TNF-α treatment in MCF-7 cells while it did not change in MCF-7/MX cells. TNF-α treatment along with inhibition of Akt phosphorylation by a chemical inhibitor triciribine, sensitized MCF-7 cells to cytotoxic effects of TNF-α. Moreover, activation of PI3K/Akt pathway by activator peptide 740 Y-P in MCF-7/MX cells enhanced resistance against TNF-α cytotoxicity.
  
  
  CONCLUSIONS
  Alteration in Akt phosphorylation is involved in the resistance of MCF-7 cells and sensitivity of MCF-7/MX cells to TNF-α -induced cytotoxicity, respectively.
authors.affiliation: Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.|Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Morteza
authors.initials: M
authors.lastname: Ghandadi
authors.affiliation: Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Negin
authors.initials: N
authors.lastname: Haj-Ali
authors.affiliation: Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.|Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Javad
authors.initials: J
authors.lastname: Behravan
authors.affiliation: Pharmaceutical Research Center, Department of Medicinal Chemistry, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Khalil
authors.initials: K
authors.lastname: Abnous
authors.affiliation: Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Atieh
authors.initials: A
authors.lastname: Mohammadi
authors.affiliation: Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Melika Ehtesham
authors.initials: ME
authors.lastname: Gharaee
authors.affiliation: Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.|Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Mosaffa
mesh_terms: D000970:Antineoplastic Agents; D002470:Cell Survival / Q000187:drug effects*; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006801:Humans; D061986:MCF-7 Cells; D008942:Mitoxantrone; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012263:Ribonucleosides / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D012263:Ribonucleosides; D014409:Tumor Necrosis Factor-alpha; C023764:triciribine; D008942:Mitoxantrone; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt
keywords: PI3K/Akt; Tumor necrosis factor-α; cancer; multidrug resistance