img
Ouabain Targets the Unfolded Protein Response for Selective Killing of HepG2 Cells During Glucose Deprivation        
Yazarlar
Tülay Özdemir
Rukiye Nar
Pamukkale Üniversitesi, Türkiye
Veli Kılınç
Türkiye
Hasan Alaçam
Türkiye
Osman Saliş
Aynur Düzgün
Doç. Dr. Sedat GÜLTEN
Kastamonu Üniversitesi, Türkiye
Abdülkerim Bedir
Özet
Ouabain is a cardiotonic steroid and specific inhibitor of the Na +/K+-ATPase. The relationship between ouabain treatment and the unfolded protein response (UPR) in cells is not precisely understood. Therefore, we studied the possible effects of ouabain on proliferation, apoptosis, and the UPR. HepG2 cells were cultured overnight and then treated with various concentrations of ouabain (0.75 to 750nM) in the absence or presence of 10mM 2-deoxyglucose (2-DG) for 48 hours. We also used real-time polymerase chain reaction to obtain quantitative measurements of expression levels of Grp78, Grp94, CHOP, MTJ-1, HKII, MDR-1, MRP-1, HO-1, and Par-4. Cell number, viability, and proliferation of HepG2 cells were monitored with a real-time cell analyzer system (xCELLigence). We show that ouabain modulates the UPR transcription program and induces cell death in glucose-deprived tumor cells. Ouabain at all concentrations showed no cytotoxicity whereas all concentrations were very effective under 2-DG stress conditions. Our findings show that disruption of the UPR during glucose deprivation could be an attractive approach for selective cancer cell killing and could provide a chemical basis for developing UPR-targeting drugs against solid tumors. Ouabain use as an adjunct to conventional cancer therapy also warrants vigorous investigation. © Copyright 2012, Mary Ann Liebert, Inc. 2012.
Anahtar Kelimeler
2-deoxyglucose | CHOP | Grp78 | HepG2 | ouabain | unfolded protein response
Makale Türü Özgün Makale
Makale Alt Türü SSCI, AHCI, SCI, SCI-Exp dergilerinde yayımlanan tam makale
Dergi Adı CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS
Dergi ISSN 1084-9785
Dergi Tarandığı Indeksler SCI-Expanded
Makale Dili İngilizce
Basım Tarihi 10-2012
Cilt No 27
Sayı 8
Sayfalar 457 / 463
Doi Numarası 10.1089/cbr.2011.1138
Makale Linki http://dx.doi.org/10.1089/cbr.2011.1138