Relation of Metal-Binding Property and Selective Toxicity of 8-Hydroxyquinoline Derived Mannich Bases Targeting Multidrug Resistant Cancer Cells
| Autor: | Gergely Szakács, Norbert Szoboszlai, Veronika F.S. Pape, István Szatmári, Éva A. Enyedy, Christina Streli, Nóra Kucsma, Ferenc Fülöp, Anikó Gaál |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cancer Research medicine.disease_cause metal-based drugs lcsh:RC254-282 Article collateral sensitivity 03 medical and health sciences 0302 clinical medicine multidrug resistance medicine cancer chemistry.chemical_classification reactive oxygen species Reactive oxygen species Ligand Cancer medicine.disease lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens 3. Good health Multiple drug resistance 030104 developmental biology Oncology chemistry Biochemistry 030220 oncology & carcinogenesis Cancer cell Toxicity Intracellular Oxidative stress |
| Zdroj: | Cancers, Vol 13, Iss 154, p 154 (2021) Cancers Volume 13 Issue 1 |
| ISSN: | 2072-6694 |
| Popis: | Resistance to chemotherapeutic agents is a major obstacle in cancer treatment. A recently proposed strategy is to target the collateral sensitivity of multidrug resistant (MDR) cancer. Paradoxically, the toxicity of certain metal chelating agents is increased, rather than decreased, by the function of P-glycoprotein (Pgp), which is known to confer resistance by effluxing chemotherapeutic compounds from cancer cells. We have recently characterized and compared the solution&rsquo s chemical properties including ligand protonation and the metal binding properties of a set of structurally related 8-hydroxyquinoline derived Mannich bases. Here we characterize the impact of the solution stability and redox activity of their iron(III) and copper(II) complexes on MDR-selective toxicity. Our results show that the MDR-selective anticancer activity of the studied 8-hydroxyquinoline derived Mannich bases is associated with the iron deprivation of MDR cells and the preferential formation of redox-active copper(II) complexes, which undergo intracellular redox-cycling to induce oxidative stress. |
| Databáze: | OpenAIRE |
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