Zinc supplementation induces apoptosis and enhances antitumor efficacy of docetaxel in non-small-cell lung cancer
| Autor: | Firat Soyarat, Hilal Kocdor, Hakan Cengiz, Ruksan Cehreli, Duygu Harmanci, Suleyman Aydin, Mehmet Ali Kocdor, Halil Ateş, Pinar Kemanli |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Lung Neoplasms
Cell Survival Pharmaceutical Science chemistry.chemical_element Antineoplastic Agents Apoptosis Zinc Docetaxel Pharmacology Biology medicine.disease_cause chemistry.chemical_compound Inhibitory Concentration 50 A549 Carcinoma Non-Small-Cell Lung Cell Line Tumor Malondialdehyde Drug Discovery medicine Humans H1299 Cytotoxicity Lung cancer Original Research Drug Design Development and Therapy Dose-Response Relationship Drug zinc Drug Synergism medicine.disease lung cancer Oxidative Stress chemistry Cancer cell Taxoids Growth inhibition Tumor Suppressor Protein p53 Oxidative stress medicine.drug |
| Zdroj: | Drug Design, Development and Therapy |
| ISSN: | 1177-8881 |
| Popis: | Hilal Kocdor,1,2 Halil Ates,1 Suleyman Aydin,3 Ruksan Cehreli,1 Firat Soyarat,2 Pinar Kemanli,2 Duygu Harmanci,2 Hakan Cengiz,2 Mehmet Ali Kocdor4 1Institute of Oncology, Dokuz Eylul University, 2Department of Molecular Medicine, Institute of Health Sciences, Dokuz Eylul University, Izmir Turkey; 3Department of Biochemistry, Firat University School of Medicine, Elazig, 4Department of Surgery, School of Medicine, Dokuz Eylul University, Izmir, Turkey Background: Exposure to exogenous zinc results in increased apoptosis, growth inhibition, and altered oxidative stress in cancer cells. Previous studies also suggested that zinc sensitizes some cancer cells to cytotoxic agents depending on the p53 status. Therefore, zinc supplementation may show anticancer efficacy solely and may increase docetaxel-induced cytotoxicity in non-small-cell lung cancer cells.Methods: Here, we report the effects of several concentrations of zinc combined with docetaxel on p53-wild-type (A549) and p53-null (H1299) cells. We evaluated cellular viability, apoptosis, and cell cycle progression as well as oxidative stress parameters, including superoxide dismutase, glutathione peroxidase, and malondialdehyde levels.Results: Zinc reduced the viability of A549 cells and increased the apoptotic response in both cell lines in a dose-dependent manner. Zinc also amplified the docetaxel effects and reduced its inhibitory concentration 50 (IC50) values. The superoxide dismutase levels increased in all treatment groups; however, glutathione peroxidase was slightly increased in the combination treatments. Zinc also caused malondialdehyde elevations at 50µM and 100µM.Conclusion: Zinc has anticancer efficacy against non-small-cell lung cancer cells in the presence of functionally active p53 and enhances docetaxel efficacy in both p53-wild-type and p53-deficient cancer cells. Keywords: lung cancer, zinc, docetaxel, A549, H1299 |
| Databáze: | OpenAIRE |
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