Affiliations: [a] Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran | [b] Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran | [c] Pharmaceutical Research Center, Department of Medicinal Chemistry, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
Correspondence:
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Corresponding author: Fatemeh Mosaffa, School of Pharmacy, Mashhad University of Medical Sciences, P.O. Box 91775-1365, Mashhad, Iran. Tel.: +98 51 38823255; Fax: +98 51 38823251; E-mail:mosaffaf@mums.ac.ir
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. 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.
