Combination of esomeprazole with chemotherapeutics results in more pronounced cytotoxic effect via apoptosis on A549 nonsmall-cell lung cancer cell line
| Autor: | Güven Özkaya, Haluk Barbaros Oral, Seniz Korkmaz, Engin Ulukaya, Arzu Yilmaztepe Oral, Buse Cevatemre, Mehmet Sarimahmut |
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| Přispěvatelé: | Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyokimya Anabilim Dalı., Uludağ Üniversitesi/Tıp Fakültesi/İmmünoloji Anabilim Dalı., Uludağ Üniversitesi/Fen Edebiyat Fakültesi/Biyoloji Bölümü., Uludağ Üniversitesi/Tıp Fakültesi/Biyoistatistik Anabilim Dalı., Yılmaztepe, Oral Arzu, Oral, Haluk Barbaros, Sarımahmut, Mehmet, Cevatemre, Buse, Özkaya, Güven, Korkmaz, Şeniz, Ulukaya, Engin, K-7285-2012, AAG-8288-2021, A-4421-2016, K-5792-2018 |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Proton pump inhibitors Physiology Resistance Apoptosis Pharmacology Biology Vinorelbine Microbiology Carboplatin Esomeprazole 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Solid tumors Lung carcinoma cisplatin carboplatin esomeprazole apoptosis synergism Lung carcinoma Genetics medicine Pharmacokinetics Cytotoxicity Molecular Biology Breast-cancer Life sciences & biomedicine - other topics Cisplatin Drug-combination Ph Synergism Human-melanoma Cell Biology Gemcitabine Tumor acidity Vacuolar h+-atpase H-Transporting ATP Synthase Proton Pump Inhibitors Bafilomycin A1 030104 developmental biology chemistry Paclitaxel Docetaxel 030220 oncology & carcinogenesis General Agricultural and Biological Sciences medicine.drug |
| Zdroj: | Volume: 41, Issue: 1 231-241 Turkish Journal of Biology |
| ISSN: | 1300-0152 1303-6092 |
| Popis: | 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 determination of PARP cleavage in western blotting. 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. |
| Databáze: | OpenAIRE |
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