Benzoxazole-based Zn(II) and Cu(II) Complexes Overcome Multidrug-resistance in Cancer
| Autor: | Hiroshi Sekiya, Borisz Varga, Gabriella Spengler, Bálint Rácz, Jun Maki, Joseph Molnár, Ryosuke Saijo, Genki Watanabe, Masami Kawase, Eiji Tamai, Annamária Kincses |
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| Rok vydání: | 2018 |
| Předmět: |
Cancer Research
ATP Binding Cassette Transporter Subfamily B Lymphoma T-Cell Transfection 010402 general chemistry 01 natural sciences Rhodamine 123 Mice chemistry.chemical_compound Coordination Complexes Cell Line Tumor Animals Cytotoxic T cell Propidium iodide P-glycoprotein biology 010405 organic chemistry Chemistry Ligand General Medicine Molecular biology Drug Resistance Multiple 0104 chemical sciences Multiple drug resistance Zinc Oncology Drug Resistance Neoplasm Apoptosis biology.protein Copper |
| Zdroj: | Anticancer Research. 38:6181-6187 |
| ISSN: | 1791-7530 0250-7005 |
| Popis: | Background/aim Multidrug resistance (MDR) represents a significant impediment to successful cancer treatment. In this study, novel metal [Zn(II), Cu(II), Mg(II), Ni(II), Pd(II), and Ag(I)] complexes of 2-trifluoroacetonylbenzoxazole previously synthesized and characterized by our group were tested for their MDR-reversing activity in comparison with the free ligands in L5178Y mouse T-lymphoma (MDR) cells transfected with human ATP-binding cassette sub-family B member 1 (ABCB1; P-glycoprotein) gene. Materials and methods Cytotoxic and antiproliferative effects of the complexes were assessed by the thiazolyl blue tetrazolium bromide (MTT) method. Modulation of ABCB1 activity was measured by rhodamine 123 accumulation assay using flow cytometry. The apoptosis-inducing activity of some complexes was also tested on the multidrug resistant L5178Y mouse T-lymphoma cells, using the annexin-V/propidium iodide assay. Results When compared to the free ligand, a remarkable enhancement in MDR reversal and cytotoxic activity was found for the Zn(II) and Cu(II) complexes. The activity of the complexes proved to be up to 29- and 5-fold higher than that of the ligands and the ABCB1 inhibitor verapamil as positive control, respectively. The complexes possessed a remarkable potential to induce apoptosis of MDR cells. Conclusion Our results suggest that the Zn(II) and Cu(II) complexes display significant MDR-reversing activity in a dose-dependent manner and possess strong cytotoxic activity and a remarkable potential to induce apoptosis in MDR L5178Y mouse T-lymphoma cells. |
| Databáze: | OpenAIRE |
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