The cells treated with the cisplatin and esomeprazole combination displayed characteristic features of apoptosis such as elevated M30 levels, Annexin-V staining and PARP cleavage. In conclusion, these novel combinations resulted in higher sensitivity of tumors to chemotherapeutics, thereby warranting further in vivo experiments for proof of the concept. | Turkish Journal of Biology Turk J Biol (2017) 41: 231-241 © TÜBİTAK doi: Research Article Combination of esomeprazole with chemotherapeutics results in more pronounced cytotoxic effect via apoptosis on A549 nonsmall-cell lung cancer cell line 1 2 3 Arzu YILMAZTEPE ORAL , Haluk Barbaros ORAL , Mehmet SARIMAHMUT , 3 4 1 1, Buse CEVATEMRE , Güven ÖZKAYA , Şeniz KORKMAZ , Engin ULUKAYA * 1 Department of Medical Biochemistry, Faculty of Medicine, Uludağ University, Bursa, Turkey 2 Department of Immunology, Faculty of Medicine, Uludağ University, Bursa, Turkey 3 Department of Biology, Faculty of Arts and Sciences, Uludağ University, Bursa, Turkey 4 Department of Biostatistics, Faculty of Medicine, Uludağ University, Bursa, Turkey Received: Accepted/Published Online: Final Version: Abstract: The vacuolar (H+)-ATPases that pump H+ from the cytoplasm to extracellular compartments can alter the pH of the tumor microenvironment. Esomeprazole can effectively inhibit vacuolar (H+)-ATPases and may increase the effectiveness of chemotherapeutics. Therefore, we used esomeprazole in combination with cisplatin, carboplatin, paclitaxel, docetaxel, gemcitabine, and vinorelbine on the A549 nonsmall-cell lung cancer cell line. Cisplatin and carboplatin combinations with esomeprazole exhibited superior cytotoxicity compared to the other selected chemotherapeutics. Low-dose combinations of esomeprazole with either cisplatin or carboplatin resulted in synergistic interaction. We examined cytotoxic activity of these combinations with the xCELLigence real-time cytotoxicity assay and detected that esomeprazole combinations with both 100% test drug concentrations of cisplatin and carboplatin shifted the antiproliferative effects of these agents towards a cytotoxic effect in a dose-dependent manner. Cell death mode was investigated by M30 assay, Annexin-V-FITC fluorescence imaging, and .
