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Do iron chelators increase the antiproliferative effect of trichostatin A through a glucose-regulated protein 78 mediated mechanism?      
Yazarlar
Veli Kılınç
Türkiye
Abdülkerim Bedir
Ali Okuyucu
Osman Saliş
Hasan Alaçam
Doç. Dr. Sedat GÜLTEN
Kastamonu Üniversitesi, Türkiye
Özet
Histone deacetylase (HDAC) inhibitors, such as trichostatin A (TSA), and iron chelators, including deferoxamine (DFO) and phenanthroline (PHEN), appear to have anticancer effects. We hypothesized that the HDAC inhibitors and iron chelators would be synergistic with their effect on breast cancer cell line MCF7, because the HDAC inhibitors increase glucose-regulated protein 78 (Grp78) and the iron chelators reduce its expression. Although the administration of TSA alone resulted in a dose-related decrease in the cell index, it did not have an antiproliferative effect except the 62.5 and 500 nM of TSA. However, all doses of TSA produced a cytotoxic effect from the initial hours when combined with 150 μM of DFO and 25 μM of PHEN. DFO and PHEN downregulated Grp78, Grp94, and MRP1 expressions and upregulated CHOP and HO-1 expressions. TSA upregulated all the genes in various rates when used alone but resulted in decreased expression levels when combined with DFO and PHEN. Increased HDAC-1 levels in the Grp78 promoter region indicated that DFO and PHEN either promoted binding of HDAC-1 to this region or inhibited its detachment. We determined that the reduction of increased Grp78, Grp94, HO-1, and MRP1 expressions, which appears to inhibit the chemotherapeutic effect of TSA, through the combination with DFO or PHEN will contribute to the anticancer effect. © 2014 International Society of Oncology and BioMarkers (ISOBM).
Anahtar Kelimeler
MCF-7,Trichostatin A,Deferoxamine,Phenanthroline,Grp78,CHOP
Makale Türü Özgün Makale
Makale Alt Türü SSCI, AHCI, SCI, SCI-Exp dergilerinde yayımlanan tam makale
Dergi Adı Tumor Biology
Dergi ISSN 1010-4283
Dergi Tarandığı Indeksler SCI-Expanded
Makale Dili İngilizce
Basım Tarihi 06-2014
Cilt No 35
Sayı 6
Sayfalar 5945 / 5951
Doi Numarası 10.1007/s13277-014-1788-1
Makale Linki http://dx.doi.org/10.1007/s13277-014-1788-1