{"doi":"10.1093/mtomcs/mfab074","title":"The ionophore thiomaltol induces rapid lysosomal accumulation of copper and apoptosis in melanoma","abstract":"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.","journal":"Metallomics","year":2021,"id":185602,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9536,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":475716,"name":"Long Dao","orcid":"0000-0002-7857-3242","position":1,"is_corresponding":false},{"id":507605,"name":"M. Karen Newell‐Rogers","orcid":null,"position":2,"is_corresponding":false},{"id":742796,"name":"Babbak Shahandeh","orcid":null,"position":3,"is_corresponding":false},{"id":442102,"name":"Frank L. Meyskens","orcid":"0000-0002-8827-4334","position":4,"is_corresponding":false},{"id":742797,"name":"Susan Kurumi Kozawa","orcid":null,"position":5,"is_corresponding":false},{"id":442103,"name":"Feng Liu","orcid":"0000-0003-3963-0651","position":6,"is_corresponding":false},{"id":639959,"name":"Germán Plascencia‐Villa","orcid":"0000-0002-5955-437X","position":7,"is_corresponding":false},{"id":72878,"name":"Miguel José Yacamán","orcid":"0000-0002-2945-6509","position":8,"is_corresponding":false},{"id":240323,"name":"Shang Jia","orcid":"0000-0001-6285-8959","position":9,"is_corresponding":false},{"id":240330,"name":"Christopher J. Chang","orcid":"0000-0001-5732-9497","position":10,"is_corresponding":false},{"id":738541,"name":"Patrick J. Farmer","orcid":"0000-0001-9911-999X","position":11,"is_corresponding":false},{"id":738537,"name":"Ottis Scrivner","orcid":"0000-0002-1358-8902","position":0,"is_corresponding":true}],"reference_count":71,"raw_metadata":null,"created_at":"2026-07-18T23:48:38.805613Z","pmid":"34958363","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}