{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:57:08Z","timestamp":1791928628204,"version":"4.3.4"},"reference-count":45,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2021,4,14]],"date-time":"2021-04-14T00:00:00Z","timestamp":1618358400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,4,14]],"date-time":"2021-04-14T00:00:00Z","timestamp":1618358400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100009148","name":"Queen Mary University of London","doi-asserted-by":"publisher","award":["Incentivisation Award"],"award-info":[{"award-number":["Incentivisation Award"]}],"id":[{"id":"10.13039\/100009148","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009148","name":"Queen Mary University of London","doi-asserted-by":"publisher","award":["Incentivisation Award"],"award-info":[{"award-number":["Incentivisation Award"]}],"id":[{"id":"10.13039\/100009148","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Barts Charity Strategic Research Grant"},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C41405\/A19694"],"award-info":[{"award-number":["C41405\/A19694"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C41405\/A19694"],"award-info":[{"award-number":["C41405\/A19694"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C41405\/A19694"],"award-info":[{"award-number":["C41405\/A19694"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C41405\/A19694"],"award-info":[{"award-number":["C41405\/A19694"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C41405\/A13034"],"award-info":[{"award-number":["C41405\/A13034"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Death Dis"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>High-grade serous cancer (HGSC) accounts for ~67% of all ovarian cancer deaths. Although initially sensitive to platinum chemotherapy, resistance is inevitable and there is an unmet clinical need for novel therapies that can circumvent this event. We performed a drug screen with 1177 FDA-approved drugs and identified the hydroxyquinoline drug, chloroxine. In extensive validation experiments, chloroxine restored sensitivity to both cisplatin and carboplatin, demonstrating broad synergy in our range of experimental models of platinum-resistant HGSC. Synergy was independent of chloroxine\u2019s predicted ionophore activity and did not relate to platinum uptake as measured by atomic absorption spectroscopy. Further mechanistic investigation revealed that chloroxine overrides DNA damage tolerance in platinum-resistant HGSC. Co-treatment with carboplatin and chloroxine (but not either drug alone) caused an increase in \u03b3H2AX expression, followed by a reduction in platinum-induced RAD51 foci. Moreover, this unrepaired DNA damage was associated with p53 stabilisation, cell cycle re-entry and triggering of caspase 3\/7-mediated cell death. Finally, in our platinum-resistant, intraperitoneal in vivo model, treatment with carboplatin alone resulted in a transient tumour response followed by tumour regrowth. In contrast, treatment with chloroxine and carboplatin combined, was able to maintain tumour volume at baseline for over 4 months. In conclusion, our novel results show that chloroxine facilitates platinum-induced DNA damage to restore platinum sensitivity in HGSC. Since chloroxine is already licensed, this exciting combination therapy could now be rapidly translated for patient benefit.<\/jats:p>","DOI":"10.1038\/s41419-021-03665-0","type":"journal-article","created":{"date-parts":[[2021,4,14]],"date-time":"2021-04-14T06:03:10Z","timestamp":1618380190000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Chloroxine overrides DNA damage tolerance to restore platinum sensitivity in high-grade serous ovarian cancer"],"prefix":"10.1038","volume":"12","author":[{"given":"Vera L.","family":"Silva","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayeta","family":"Saxena","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Nicolini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph I.","family":"Hoare","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Metcalf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3321-6601","authenticated-orcid":false,"given":"Sarah A.","family":"Martin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9281-5789","authenticated-orcid":false,"given":"Michelle","family":"Lockley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,4,14]]},"reference":[{"key":"3665_CR1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-019-6139-6","volume":"19","author":"Y Zhang","year":"2019","unstructured":"Zhang, Y. et al. Global patterns and trends in ovarian cancer incidence: age, period and birth cohort analysis. BMC Cancer 19, 984 (2019).","journal-title":"BMC Cancer"},{"key":"3665_CR2","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1097\/PAT.0b013e328348a6e7","volume":"43","author":"WG McCluggage","year":"2011","unstructured":"McCluggage, W. G. Morphological subtypes of ovarian carcinoma: a review with emphasis on new developments and pathogenesis. Pathology 43, 420\u201332 (2011).","journal-title":"Pathology"},{"key":"3665_CR3","doi-asserted-by":"publisher","DOI":"10.1186\/s13048-019-0484-6","volume":"12","author":"A Gadducci","year":"2019","unstructured":"Gadducci, A. et al. Current strategies for the targeted treatment of high-grade serous epithelial ovarian cancer and relevance of BRCA mutational status. J. Ovarian Res. 12, 9 (2019).","journal-title":"J. Ovarian Res."},{"key":"3665_CR4","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1038\/nrc4019","volume":"15","author":"DD Bowtell","year":"2015","unstructured":"Bowtell, D. D. et al. Rethinking ovarian cancer II: reducing mortality from high-grade serous ovarian cancer. Nat. Rev. Cancer 15, 668\u201379 (2015).","journal-title":"Nat. Rev. Cancer"},{"key":"3665_CR5","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1016\/j.bbagen.2018.11.005","volume":"1863","author":"M Binju","year":"2019","unstructured":"Binju, M. et al. Mechanisms underlying acquired platinum resistance in high grade serous ovarian cancer\u2014a mini review. Biochimica et. Biophysica Acta 1863, 371\u20138 (2019).","journal-title":"Biochimica et. Biophysica Acta"},{"key":"3665_CR6","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1089\/cbr.2009.0701","volume":"25","author":"JH Ren","year":"2010","unstructured":"Ren, J. H. et al. Acquired cisplatin resistance in human lung adenocarcinoma cells is associated with enhanced autophagy. Cancer Biother Radiopharm. 25, 75\u201380 (2010).","journal-title":"Cancer Biother Radiopharm."},{"key":"3665_CR7","doi-asserted-by":"publisher","first-page":"1869","DOI":"10.1038\/onc.2011.384","volume":"31","author":"L Galluzzi","year":"2012","unstructured":"Galluzzi, L. et al. Molecular mechanisms of cisplatin resistance. Oncogene 31, 1869\u201383 (2012).","journal-title":"Oncogene"},{"key":"3665_CR8","doi-asserted-by":"publisher","first-page":"1109","DOI":"10.1038\/bjc.1992.419","volume":"66","author":"SY Loh","year":"1992","unstructured":"Loh, S. Y., Mistry, P., Kelland, L. R., Abel, G. & Harrap, K. R. Reduced drug accumulation as a major mechanism of acquired resistance to cisplatin in a human ovarian carcinoma cell line: circumvention studies using novel platinum (II) and (IV) ammine\/amine complexes. Br. J. Cancer 66, 1109\u201315 (1992).","journal-title":"Br. J. Cancer"},{"key":"3665_CR9","first-page":"1","volume":"4","author":"D Fink","year":"1998","unstructured":"Fink, D., Aebi, S. & Howell, S. B. The role of DNA mismatch repair in drug resistance. Clin. Cancer Res. 4, 1\u20136 (1998).","journal-title":"Clin. Cancer Res."},{"key":"3665_CR10","doi-asserted-by":"publisher","first-page":"927","DOI":"10.1124\/mol.109.058131","volume":"76","author":"WP Roos","year":"2009","unstructured":"Roos, W. P. et al. The translesion polymerase Rev3L in the tolerance of alkylating anticancer drugs. Mol. Pharmacol. 76, 927 (2009).","journal-title":"Mol. Pharmacol."},{"key":"3665_CR11","first-page":"390","volume":"23","author":"A Gadducci","year":"2002","unstructured":"Gadducci, A., Cosio, S., Muraca, S. & Genazzani, A. R. Molecular mechanisms of apoptosis and chemosensitivity to platinum and paclitaxel in ovarian cancer: biological data and clinical implications. Eur. J. Gynaecol. Oncol. 23, 390\u20136 (2002).","journal-title":"Eur. J. Gynaecol. Oncol."},{"key":"3665_CR12","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1038\/s43018-019-0018-6","volume":"1","author":"SM Corsello","year":"2020","unstructured":"Corsello, S. M. et al. Discovering the anticancer potential of non-oncology drugs by systematic viability profiling. Nat. Cancer 1, 235\u2013\u2013248 (2020).","journal-title":"Nat. Cancer"},{"key":"3665_CR13","doi-asserted-by":"crossref","unstructured":"Hoare J. I. et al. Platinum resistance induces diverse evolutionary trajectories in high grade serous ovarian cancer. Preprint at https:\/\/www.biorxiv.org\/content\/10.1101\/2020.07.23.200378v1 (2020).","DOI":"10.1101\/2020.07.23.200378"},{"key":"3665_CR14","doi-asserted-by":"publisher","first-page":"118042","DOI":"10.1016\/j.saa.2020.118042","volume":"230","author":"N Shahabadi","year":"2020","unstructured":"Shahabadi, N. & Zendehcheshm, S. Evaluation of ct-DNA and HSA binding propensity of antibacterial drug chloroxine: multi-spectroscopic analysis, atomic force microscopy and docking simulation. Spectrochim. Acta A Mol. Biomol. Spectrosc. 230, 118042 (2020).","journal-title":"Spectrochim. Acta A Mol. Biomol. Spectrosc."},{"key":"3665_CR15","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1002\/emmm.200900040","volume":"1","author":"SA Martin","year":"2009","unstructured":"Martin, S. A. et al. Methotrexate induces oxidative DNA damage and is selectively lethal to tumour cells with defects in the DNA mismatch repair gene MSH2. EMBO Mol. Med. 1, 323\u201337 (2009).","journal-title":"EMBO Mol. Med."},{"key":"3665_CR16","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1016\/j.ijpharm.2016.04.027","volume":"506","author":"M Najlah","year":"2016","unstructured":"Najlah, M. et al. Novel paclitaxel formulations solubilized by parenteral nutrition nanoemulsions for application against glioma cell lines. Int. J. Pharmaceutics 506, 102\u20139 (2016).","journal-title":"Int. J. Pharmaceutics"},{"key":"3665_CR17","doi-asserted-by":"publisher","first-page":"1636","DOI":"10.1158\/0008-5472.CAN-06-3546","volume":"67","author":"D Chen","year":"2007","unstructured":"Chen, D. et al. Clioquinol, a therapeutic agent for alzheimers disease, has proteasome-inhibitory, androgen receptor\u2013suppressing, apoptosis-inducing, and antitumor activities in human prostate cancer cells and xenografts. Cancer Res. 67, 1636 (2007).","journal-title":"Cancer Res."},{"key":"3665_CR18","doi-asserted-by":"publisher","DOI":"10.1186\/bcr1322","volume":"7","author":"KG Daniel","year":"2005","unstructured":"Daniel, K. G. et al. Clioquinol and pyrrolidine dithiocarbamate complex with copper to form proteasome inhibitors and apoptosis inducers in human breast cancer cells. Breast Cancer Res. 7, R897 (2005).","journal-title":"Breast Cancer Res."},{"key":"3665_CR19","unstructured":"Chou, D. & Martin, N. J.. CfDCPS, synergism UsGACPfQo, antagonism in drug combinations, IC50 tDo, ED50. ComboSyn Inc Paramus NJ. (2005).Accessed Dec 2020. https:\/\/www.combosyn.com\/."},{"key":"3665_CR20","doi-asserted-by":"publisher","first-page":"3389","DOI":"10.1158\/0008-5472.CAN-04-3577","volume":"65","author":"WQ Ding","year":"2005","unstructured":"Ding, W. Q., Liu, B., Vaught, J. L., Yamauchi, H. & Lind, S. E. Anticancer activity of the antibiotic clioquinol. Cancer Res. 65, 3389\u201395 (2005).","journal-title":"Cancer Res."},{"key":"3665_CR21","doi-asserted-by":"publisher","first-page":"10448","DOI":"10.1021\/jm301053a","volume":"55","author":"S Tardito","year":"2012","unstructured":"Tardito, S. et al. Copper-dependent cytotoxicity of 8-hydroxyquinoline derivatives correlates with their hydrophobicity and does not require caspase activation. J. Med Chem. 55, 10448\u201359 (2012).","journal-title":"J. Med Chem."},{"key":"3665_CR22","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1007\/s00775-009-0594-5","volume":"15","author":"S Zhai","year":"2010","unstructured":"Zhai, S. et al. Tumor cellular proteasome inhibition and growth suppression by 8-hydroxyquinoline and clioquinol requires their capabilities to bind copper and transport copper into cells. JBIC J. Biol. Inorg. Chem. 15, 259\u201369 (2010).","journal-title":"JBIC J. Biol. Inorg. Chem."},{"key":"3665_CR23","first-page":"2087","volume":"30","author":"H Yu","year":"2010","unstructured":"Yu, H., Lou, J. R. & Ding, W.-Q. Clioquinol independently targets NF-\u03baB and lysosome pathways in human cancer cells. Anticancer Res. 30, 2087\u20132092 (2010).","journal-title":"Anticancer Res."},{"key":"3665_CR24","doi-asserted-by":"crossref","unstructured":"Xiao, M. et al. Comparison of different sample preparation methods for platinum determination in cultured cells by graphite furnace atomic absorption spectrometry. PeerJ 5, e2873 (2017).","DOI":"10.7717\/peerj.2873"},{"key":"3665_CR25","unstructured":"PubChem [Internet]. Bethesda (MD): National Library of Medicine (US), National Center for Biotechnology Information; 2004-. PubChem Compound Summary for CID 2722, Chloroxine. Available from: https:\/\/pubchem.ncbi.nlm.nih.gov\/compound\/Chloroxine."},{"key":"3665_CR26","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1038\/s43018-019-0018-6","volume":"1","author":"SM Corsello","year":"2020","unstructured":"Corsello, S. M. et al. Discovering the anticancer potential of non-oncology drugs by systematic viability profiling. Nat. Cancer 1, 235\u201348 (2020).","journal-title":"Nat. Cancer"},{"key":"3665_CR27","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0070701","volume":"8","author":"TA Munro","year":"2013","unstructured":"Munro, T. A. et al. Selective kappa opioid antagonists nor-BNI, GNTI and JDTic have low affinities for non-opioid receptors and transporters. PLoS ONE 8, e70701 (2013).","journal-title":"PLoS ONE"},{"key":"3665_CR28","doi-asserted-by":"publisher","first-page":"4532","DOI":"10.1158\/1078-0432.CCR-10-0523","volume":"16","author":"CE Redon","year":"2010","unstructured":"Redon, C. E. et al. Histone \u03b3H2AX and poly (ADP-ribose) as clinical pharmacodynamic biomarkers. Clin. Cancer Res. 16, 4532\u20134542 (2010).","journal-title":"Clin. Cancer Res."},{"key":"3665_CR29","doi-asserted-by":"publisher","first-page":"1480","DOI":"10.1016\/j.bcp.2009.02.002","volume":"77","author":"ER Tuller","year":"2009","unstructured":"Tuller, E. R. et al. PPAR\u03b1 signaling mediates the synergistic cytotoxicity of clioquinol and docosahexaenoic acid in human cancer cells. Biochem. Pharmacol. 77, 1480\u20136 (2009).","journal-title":"Biochem. Pharmacol."},{"key":"3665_CR30","doi-asserted-by":"publisher","first-page":"3605","DOI":"10.1038\/onc.2014.296","volume":"34","author":"Y Yang-Hartwich","year":"2015","unstructured":"Yang-Hartwich, Y. et al. p53 protein aggregation promotes platinum resistance in ovarian cancer. Oncogene 34, 3605\u201316 (2015).","journal-title":"Oncogene"},{"key":"3665_CR31","doi-asserted-by":"publisher","first-page":"1169","DOI":"10.1016\/S1470-2045(11)70123-1","volume":"12","author":"SL Cooke","year":"2011","unstructured":"Cooke, S. L. & Brenton, J. D. Evolution of platinum resistance in high-grade serous ovarian cancer. Lancet Oncol. 12, 1169\u201374 (2011).","journal-title":"Lancet Oncol."},{"key":"3665_CR32","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1038\/nature10166","volume":"474","author":"Network CGAR.","year":"2011","unstructured":"Network CGAR. Integrated genomic analyses of ovarian carcinoma. Nature 474, 609 (2011).","journal-title":"Nature"},{"key":"3665_CR33","doi-asserted-by":"crossref","unstructured":"Damia, G. & Broggini, M. Platinum resistance in ovarian cancer: role of DNA repair. Cancers 11, 119 (2019).","DOI":"10.3390\/cancers11010119"},{"key":"3665_CR34","doi-asserted-by":"publisher","first-page":"756","DOI":"10.1002\/humu.22556","volume":"35","author":"B Leroy","year":"2014","unstructured":"Leroy, B. et al. Analysis of TP53 mutation status in human cancer cell lines: a reassessment. Hum. Mutat. 35, 756\u201365 (2014).","journal-title":"Hum. Mutat."},{"key":"3665_CR35","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms3126","volume":"4","author":"S Domcke","year":"2013","unstructured":"Domcke, S., Sinha, R., Levine, D. A., Sander, C. & Schultz, N. Evaluating cell lines as tumour models by comparison of genomic profiles. Nat. Commun. 4, 2126 (2013).","journal-title":"Nat. Commun."},{"key":"3665_CR36","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1038\/nature10166","volume":"474","author":"D Bell","year":"2011","unstructured":"Bell, D. et al. Integrated genomic analyses of ovarian carcinoma. Nature 474, 609\u201315 (2011).","journal-title":"Nature"},{"key":"3665_CR37","doi-asserted-by":"publisher","first-page":"2213","DOI":"10.1038\/s41388-017-0040-z","volume":"37","author":"D Ghannam-Shahbari","year":"2018","unstructured":"Ghannam-Shahbari, D. et al. PAX8 activates a p53-p21-dependent pro-proliferative effect in high grade serous ovarian carcinoma. Oncogene 37, 2213\u201324 (2018).","journal-title":"Oncogene"},{"key":"3665_CR38","doi-asserted-by":"publisher","first-page":"D938","DOI":"10.1093\/nar\/gkv1030","volume":"44","author":"JE Tym","year":"2015","unstructured":"Tym, J. E. et al. canSAR: an updated cancer research and drug discovery knowledgebase. Nucleic Acids Res. 44, D938\u2013D43 (2015).","journal-title":"Nucleic Acids Res."},{"key":"3665_CR39","doi-asserted-by":"crossref","first-page":"201367","DOI":"10.4061\/2010\/201367","volume":"2010","author":"A Basu","year":"2010","unstructured":"Basu, A. & Krishnamurthy, S. Cellular responses to cisplatin-induced DNA damage. J. Nucleic Acids 2010, 201367 (2010).","journal-title":"J. Nucleic Acids"},{"key":"3665_CR40","doi-asserted-by":"crossref","unstructured":"Gonzalez-Rajal, A., Hastings, J. F., Watkins, D. N., Croucher, D. R. & Burgess, A. Breathing New life into the mechanisms of platinum resistance in lung adenocarcinoma. Front. Cell Dev. Biol. 8, 305 (2020).","DOI":"10.3389\/fcell.2020.00305"},{"key":"3665_CR41","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1038\/nm.4291","volume":"23","author":"PM Bruno","year":"2017","unstructured":"Bruno, P. M. et al. A subset of platinum-containing chemotherapeutic agents kills cells by inducing ribosome biogenesis stress. Nat. Med. 23, 461\u201371 (2017).","journal-title":"Nat. Med."},{"key":"3665_CR42","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1124\/mol.119.117564","volume":"97","author":"X Xie","year":"2020","unstructured":"Xie, X., He, G. & Siddik, Z. H. Cisplatin in combination with MDM2 inhibition downregulates Rad51 recombinase in a bimodal manner to inhibit homologous recombination and augment tumor cell kill. Mol. Pharmacol. 97, 237\u2013249 (2020).","journal-title":"Mol. Pharmacol."},{"key":"3665_CR43","doi-asserted-by":"publisher","first-page":"20810","DOI":"10.1073\/pnas.0807990106","volume":"105","author":"CM Hine","year":"2008","unstructured":"Hine, C. M., Seluanov, A. & Gorbunova, V. Use of the Rad51 promoter for targeted anti-cancer therapy. Proc. Natl Acad. Sci. USA 105, 20810\u20135 (2008).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"3665_CR44","doi-asserted-by":"publisher","DOI":"10.1186\/s13048-016-0239-6","volume":"9","author":"\u00c5 Fransson","year":"2016","unstructured":"Fransson, \u00c5. et al. Strong synergy with APR-246 and DNA-damaging drugs in primary cancer cells from patients with TP53 mutant high-grade serous ovarian cancer. J. Ovarian Res. 9, 27 (2016).","journal-title":"J. Ovarian Res."},{"key":"3665_CR45","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/j.tox.2012.05.013","volume":"299","author":"M Katsuyama","year":"2012","unstructured":"Katsuyama, M. et al. Clioquinol induces DNA double-strand breaks, activation of ATM, and subsequent activation of p53 signaling. Toxicology 299, 55\u20139 (2012).","journal-title":"Toxicology"}],"container-title":["Cell Death &amp; Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41419-021-03665-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41419-021-03665-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41419-021-03665-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,28]],"date-time":"2024-08-28T08:11:14Z","timestamp":1724832674000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41419-021-03665-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,14]]},"references-count":45,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2021,4]]}},"alternative-id":["3665"],"URL":"https:\/\/doi.org\/10.1038\/s41419-021-03665-0","relation":{},"ISSN":["2041-4889"],"issn-type":[{"value":"2041-4889","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,14]]},"assertion":[{"value":"14 December 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 March 2021","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 March 2021","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 April 2021","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"This paper does not describe studies involving human participants, human data or human tissue. Institutional review board approval was obtained for animal experiments.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics statement"}},{"value":"M.L. and J.S. were supported by a Barts and The London Charity Strategic Research Grant (467\/2244). ML and VS received support from a Barts Cancer Institute Incentivisation Award. M.L., F.N., J.I.H. and S.M. were supported by ML\u2019s Cancer Research UK Advanced Clinician Scientist Fellowship (C41405\/A19694). M.L. received additional support from her Cancer Research UK Clinician Scientist Fellowship (C41405\/A13034).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Funding"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"395"}}