The ionophore thiomaltol induces rapid lysosomal accumulation of copper and apoptosis in melanoma
| Autor: | Ottis Scrivner, Long Dao, M Karen Newell-Rogers, Babbak Shahandeh, Frank L Meyskens, Susan Kurumi Kozawa, Feng Liu-Smith, Germán Plascencia-Villa, Miguel José-Yacamán, Shang Jia, Christopher J Chang, Patrick J Farmer |
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| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | Metallomics Metallomics : integrated biometal science, vol 14, iss 1 |
| ISSN: | 1756-591X |
| Popis: | In this report, we investigate the toxicity of the ionophore thiomaltol (Htma) and Cu salts to melanoma. Divalent metal complexes of thiomaltol display toxicity against A375 melanoma cell culture resulting in a distinct apoptotic response at submicromolar concentrations, with toxicity of Cu(tma)2 > Zn(tma)2 >> Ni(tma)2. In metal-chelated media, Htma treatment shows little toxicity, but the combination with supplemental CuCl2, termed Cu/Htma treatment, results in toxicity that increases with suprastoichiometric concentrations of CuCl2 and correlates with the accumulation of intracellular copper. Electron microscopy and confocal laser scanning microscopy of Cu/Htma treated cells shows a rapid accumulation of copper within lysosomes over the course of hours, concurrent with the onset of apoptosis. A buildup of ubiquitinated proteins due to proteasome inhibition is seen on the same timescale and correlates with increases of copper without additional Htma. |
| Databáze: | OpenAIRE |
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