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 |