title: Inhibition of Akt phosphorylation attenuates resistance to TNF-α cytotoxic effects in MCF-7 cells, but not in their doxorubicin resistant derivatives.
abstract: OBJECTIVE
  Acquisition of TNF-α resistance plays role in the onset and growth of malignant tumors. Previous studies have demonstrated that MCF-7 cell line and its doxorubicin resistant variant MCF-7/Adr are resistant against the cytotoxic effects of TNF-α. In this study, we investigated the role of Akt activation in resistance of MCF-7 and MCF-7/Adr against TNF-α cytotoxicity.
  
  
  METHODS
  The role of Akt activation in TNF-α cytotoxicity was investigated by MTT cell viability assay following treatment of the cells with the chemical inhibitor of Akt activation with or without TNF-α treatment. Phosphorylation of Akt at Ser473 before and after 72 hr TNF-α treatment was also determined by western blot.
  
  
  RESULTS
  TNF-α treatment led to enhancement of Akt Ser473 phosphorylation. Treatment of MCF-7 cells with TNF-α along with Akt-inhibitor agent, tricribine, attenuated Akt Ser473 phosphorylation and sensitized these cells to the cytotoxic effects of TNF-α in a dose and time dependent manner while tricribine treatment did not cause any significant cytotoxicity in MCF-7/Adr cells alone or in combination with TNF-α.
  
  
  CONCLUSIONS
  These results demonstrate that Akt phosphorylation plays pivotal role in the resistance of MCF-7 cells against TNF-α-induced cytotoxicity while it might play no significant role in the resistance of MCF-7/Adr cells against TNF-α.
authors.affiliation: 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: Atieh
authors.initials: A
authors.lastname: Mohammadi
authors.affiliation: Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran; Biotechnology Research Center, 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: Negin
authors.initials: N
authors.lastname: Haj-Ali
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: Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran; Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Mosaffa
keywords: Akt; Breast carcinoma; Multidrug resistance; Protein kinase B; Tumor necrosis factor-alpha