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TNF-α exerts higher cytotoxic effect on MCF-7 multidrug resistant derivative, role of Akt activation
Morteza Ghandadi1,2, Negin Haj-Ali2, Javad Behravan1,2
1Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
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.
Conclusion:
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.
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