{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T21:36:05Z","timestamp":1791408965743,"version":"4.3.3"},"reference-count":59,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2017,9,25]],"date-time":"2017-09-25T00:00:00Z","timestamp":1506297600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100015194","name":"Feist-Weiller Cancer Center","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100015194","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0184922","type":"journal-article","created":{"date-parts":[[2017,9,25]],"date-time":"2017-09-25T17:30:08Z","timestamp":1506360608000},"page":"e0184922","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":78,"title":["Modulating lysosomal function through lysosome membrane permeabilization or autophagy suppression restores sensitivity to cisplatin in refractory non-small-cell lung cancer cells"],"prefix":"10.1371","volume":"12","author":[{"given":"Magdalena","family":"Circu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Cardelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Barr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"O\u2019Byrne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glenn","family":"Mills","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1825-2815","authenticated-orcid":true,"given":"Hazem","family":"El-Osta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2017,9,25]]},"reference":[{"issue":"1","key":"ref1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21332","article-title":"Cancer statistics, 2016","volume":"66","author":"RL Siegel","year":"2016","journal-title":"CA Cancer J Clin"},{"issue":"11","key":"ref2","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1038\/nrc2947","article-title":"Rational, biologically based treatment of EGFR-mutant non-small-cell lung cancer","volume":"10","author":"W Pao","year":"2010","journal-title":"Nat Rev Cancer"},{"issue":"23","key":"ref3","doi-asserted-by":"crossref","first-page":"2167","DOI":"10.1056\/NEJMoa1408440","article-title":"First-line crizotinib versus chemotherapy in ALK-positive lung cancer","volume":"371","author":"BJ Solomon","year":"2014","journal-title":"N Engl J Med"},{"issue":"19","key":"ref4","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1056\/NEJMoa1606774","article-title":"Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer","volume":"375","author":"M Reck","year":"2016","journal-title":"N Engl J Med"},{"issue":"36","key":"ref5","doi-asserted-by":"crossref","first-page":"6251","DOI":"10.1200\/JCO.2009.23.5622","article-title":"American Society of Clinical Oncology Clinical Practice Guideline update on chemotherapy for stage IV non-small-cell lung cancer","volume":"27","author":"CG Azzoli","year":"2009","journal-title":"J Clin Oncol"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.ejphar.2014.07.025","article-title":"Cisplatin in cancer therapy: molecular mechanisms of action","volume":"740","author":"S Dasari","year":"2014","journal-title":"Eur J Pharmacol"},{"issue":"1","key":"ref7","doi-asserted-by":"crossref","first-page":"e54193","DOI":"10.1371\/journal.pone.0054193","article-title":"Generation and characterisation of cisplatin-resistant non-small cell lung cancer cell lines displaying a stem-like signature","volume":"8","author":"MP Barr","year":"2013","journal-title":"PLoS One"},{"issue":"2","key":"ref8","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1056\/NEJMoa011954","article-title":"Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer","volume":"346","author":"JH Schiller","year":"2002","journal-title":"N Engl J Med"},{"issue":"3","key":"ref9","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1042\/CBI20110329","article-title":"Cisplatin resistance induced by decreased apoptotic activity in non-small-cell lung cancer cell lines","volume":"36","author":"VB Cetintas","year":"2012","journal-title":"Cell Biol Int"},{"issue":"1","key":"ref10","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1089\/cbr.2009.0701","article-title":"Acquired cisplatin resistance in human lung adenocarcinoma cells is associated with enhanced autophagy","volume":"25","author":"JH Ren","year":"2010","journal-title":"Cancer Biother Radiopharm"},{"issue":"3","key":"ref11","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1124\/pr.111.005637","article-title":"Cisplatin resistance: a cellular self-defense mechanism resulting from multiple epigenetic and genetic changes","volume":"64","author":"DW Shen","year":"2012","journal-title":"Pharmacol Rev"},{"issue":"3\u20134","key":"ref12","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/j.cytogfr.2008.04.001","article-title":"Targeting the extrinsic apoptosis pathway in cancer","volume":"19","author":"A Ashkenazi","year":"2008","journal-title":"Cytokine Growth Factor Rev"},{"issue":"6","key":"ref13","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1038\/nrd3137","article-title":"Targeting mitochondria for cancer therapy","volume":"9","author":"S Fulda","year":"2010","journal-title":"Nat Rev Drug Discov"},{"issue":"1","key":"ref14","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1038\/nrm3722","article-title":"Control of apoptosis by the BCL-2 protein family: implications for physiology and therapy","volume":"15","author":"PE Czabotar","year":"2014","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"34","key":"ref15","doi-asserted-by":"crossref","first-page":"4798","DOI":"10.1038\/sj.onc.1209608","article-title":"Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy","volume":"25","author":"S Fulda","year":"2006","journal-title":"Oncogene"},{"issue":"2","key":"ref16","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.canlet.2010.05.021","article-title":"Combating apoptosis and multidrug resistant cancers by targeting lysosomes","volume":"332","author":"L Groth-Pedersen","year":"2013","journal-title":"Cancer Lett"},{"issue":"1","key":"ref17","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1073\/pnas.0408592102","article-title":"Induction of lysosomal membrane permeabilization by compounds that activate p53-independent apoptosis","volume":"102","author":"H Erdal","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"11","key":"ref18","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1038\/nrc1738","article-title":"Lysosomes and autophagy in cell death control","volume":"5","author":"G Kroemer","year":"2005","journal-title":"Nat Rev Cancer"},{"issue":"8","key":"ref19","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1038\/nrm2217","article-title":"Lysosomes: fusion and function","volume":"8","author":"JP Luzio","year":"2007","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"50","key":"ref20","doi-asserted-by":"crossref","first-page":"6434","DOI":"10.1038\/onc.2008.310","article-title":"Lysosomal membrane permeabilization in cell death","volume":"27","author":"P Boya","year":"2008","journal-title":"Oncogene"},{"issue":"8","key":"ref21","doi-asserted-by":"crossref","first-page":"2993","DOI":"10.1158\/0008-5472.CAN-05-0476","article-title":"Lysosomes as targets for cancer therapy","volume":"65","author":"N Fehrenbacher","year":"2005","journal-title":"Cancer Res"},{"issue":"4","key":"ref22","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1093\/jmcb\/mjt022","article-title":"The lysosome: from waste bag to potential therapeutic target","volume":"5","author":"H Appelqvist","year":"2013","journal-title":"J Mol Cell Biol"},{"issue":"1\u20132","key":"ref23","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1007\/s11010-011-1033-9","article-title":"Lysosomal membrane permeabilization is involved in curcumin-induced apoptosis of A549 lung carcinoma cells","volume":"359","author":"QY Chen","year":"2012","journal-title":"Mol Cell Biochem"},{"issue":"5","key":"ref24","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1593\/neo.05850","article-title":"Cardenolide-induced lysosomal membrane permeabilization demonstrates therapeutic benefits in experimental human non-small cell lung cancers","volume":"8","author":"T Mijatovic","year":"2006","journal-title":"Neoplasia"},{"issue":"1","key":"ref25","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.canlet.2015.04.028","article-title":"Enhancing therapeutic efficacy of the MEK inhibitor, MEK162, by blocking autophagy or inhibiting PI3K\/Akt signaling in human lung cancer cells","volume":"364","author":"W Yao","year":"2015","journal-title":"Cancer Lett"},{"issue":"1","key":"ref26","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1097\/CAD.0b013e32835a36db","article-title":"Chloroquine overcomes resistance of lung carcinoma cells to the dual PI3K\/mTOR inhibitor PI103 by lysosome-mediated apoptosis","volume":"24","author":"S Enzenmuller","year":"2013","journal-title":"Anticancer Drugs"},{"issue":"11","key":"ref27","doi-asserted-by":"crossref","first-page":"2682","DOI":"10.1002\/ijc.27935","article-title":"The dual PI3K\/mTOR inhibitor NVP-BEZ235 and chloroquine synergize to trigger apoptosis via mitochondrial-lysosomal cross-talk","volume":"132","author":"C Seitz","year":"2013","journal-title":"Int J Cancer"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"16087","DOI":"10.1038\/cddiscovery.2016.87","article-title":"Aquaporin 3 facilitates chemoresistance in gastric cancer cells to cisplatin via autophagy","volume":"2","author":"X Dong","year":"2016","journal-title":"Cell Death Discov"},{"issue":"3","key":"ref29","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1016\/j.ygyno.2015.03.053","article-title":"The anti-malarial chloroquine suppresses proliferation and overcomes cisplatin resistance of endometrial cancer cells via autophagy inhibition","volume":"137","author":"T Fukuda","year":"2015","journal-title":"Gynecol Oncol"},{"issue":"13","key":"ref30","doi-asserted-by":"crossref","first-page":"1566","DOI":"10.1016\/j.phymed.2016.09.003","article-title":"Immunomodulatory proteins FIP-gts and chloroquine induce caspase-independent cell death via autophagy for resensitizing cisplatin-resistant urothelial cancer cells","volume":"23","author":"IL Hsin","year":"2016","journal-title":"Phytomedicine"},{"issue":"18","key":"ref31","doi-asserted-by":"crossref","first-page":"24995","DOI":"10.18632\/oncotarget.8735","article-title":"Essential role for acid sphingomyelinase-inhibited autophagy in melanoma response to cisplatin","volume":"7","author":"D Cervia","year":"2016","journal-title":"Oncotarget"},{"issue":"1","key":"ref32","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.canlet.2014.09.020","article-title":"Induction of autophagy counteracts the anticancer effect of cisplatin in human esophageal cancer cells with acquired drug resistance","volume":"355","author":"L Yu","year":"2014","journal-title":"Cancer Lett"},{"issue":"4","key":"ref33","doi-asserted-by":"crossref","first-page":"e0126147","DOI":"10.1371\/journal.pone.0126147","article-title":"Chloroquine-enhanced efficacy of cisplatin in the treatment of hypopharyngeal carcinoma in xenograft mice","volume":"10","author":"XG Zhao","year":"2015","journal-title":"PLoS One"},{"key":"ref34","first-page":"1035","article-title":"Chloroquine enhances the efficacy of cisplatin by suppressing autophagy in human adrenocortical carcinoma treatment","volume":"10","author":"L Qin","year":"2016","journal-title":"Drug Des Devel Ther"},{"issue":"9","key":"ref35","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1038\/nrc1692","article-title":"The role of autophagy in cancer development and response to therapy","volume":"5","author":"Y Kondo","year":"2005","journal-title":"Nat Rev Cancer"},{"issue":"4","key":"ref36","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1158\/1078-0432.CCR-10-2634","article-title":"Principles and current strategies for targeting autophagy for cancer treatment","volume":"17","author":"RK Amaravadi","year":"2011","journal-title":"Clin Cancer Res"},{"issue":"11","key":"ref37","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1038\/nrm2245","article-title":"Autophagy: from phenomenology to molecular understanding in less than a decade","volume":"8","author":"DJ Klionsky","year":"2007","journal-title":"Nat Rev Mol Cell Biol"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/2049-3002-2-14","article-title":"Q&A: targeting autophagy in cancer-a new therapeutic?","volume":"2","author":"E White","year":"2014","journal-title":"Cancer Metab"},{"issue":"3","key":"ref39","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1158\/0008-5472.CAN-13-2966","article-title":"The four faces of autophagy: implications for cancer therapy","volume":"74","author":"DA Gewirtz","year":"2014","journal-title":"Cancer Res"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"12291","DOI":"10.1038\/srep12291","article-title":"Hypoxia-induced autophagy mediates cisplatin resistance in lung cancer cells","volume":"5","author":"HM Wu","year":"2015","journal-title":"Sci Rep"},{"issue":"2","key":"ref41","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.canlet.2012.07.029","article-title":"Inhibition of autophagy and induction of breast cancer cell death by mefloquine, an antimalarial agent","volume":"326","author":"N Sharma","year":"2012","journal-title":"Cancer Lett"},{"issue":"5","key":"ref42","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1158\/0008-5472.CAN-07-0562","article-title":"Blocked autophagy sensitizes resistant carcinoma cells to radiation therapy","volume":"68","author":"A Apel","year":"2008","journal-title":"Cancer Res"},{"issue":"17","key":"ref43","doi-asserted-by":"crossref","first-page":"15551","DOI":"10.18632\/oncotarget.3902","article-title":"Exploiting the potential of autophagy in cisplatin therapy: A new strategy to overcome resistance","volume":"6","author":"J Garcia-Cano","year":"2015","journal-title":"Oncotarget"},{"issue":"19","key":"ref44","doi-asserted-by":"crossref","first-page":"9177","DOI":"10.1128\/JVI.75.19.9177-9186.2001","article-title":"Additive effects characterize the interaction of antibodies involved in neutralization of the primary dualtropic human immunodeficiency virus type 1 isolate 89.6","volume":"75","author":"F Verrier","year":"2001","journal-title":"J Virol"},{"issue":"1","key":"ref45","doi-asserted-by":"crossref","first-page":"e0146931","DOI":"10.1371\/journal.pone.0146931","article-title":"A Novel High Content Imaging-Based Screen Identifies the Anti-Helminthic Niclosamide as an Inhibitor of Lysosome Anterograde Trafficking and Prostate Cancer Cell Invasion","volume":"11","author":"ML Circu","year":"2016","journal-title":"PloS one"},{"issue":"11","key":"ref46","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1101\/pdb.top070367","article-title":"Methods for Probing Lysosomal Membrane Permeabilization","volume":"2015","author":"M Jaattela","year":"2015","journal-title":"Cold Spring Harbor protocols"},{"issue":"6","key":"ref47","doi-asserted-by":"crossref","first-page":"542","DOI":"10.4161\/auto.4600","article-title":"How to interpret LC3 immunoblotting","volume":"3","author":"N Mizushima","year":"2007","journal-title":"Autophagy"},{"issue":"2","key":"ref48","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1016\/j.bbrc.2016.03.053","article-title":"Cisplatin-induced apoptosis in non-small-cell lung cancer cells is dependent on Bax- and Bak-induction pathway and synergistically activated by BH3-mimetic ABT-263 in p53 wild-type and mutant cells","volume":"473","author":"M Matsumoto","year":"2016","journal-title":"Biochem Biophys Res Commun"},{"issue":"1","key":"ref49","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1172\/JCI64180","article-title":"Lysosomal disruption preferentially targets acute myeloid leukemia cells and progenitors","volume":"123","author":"MA Sukhai","year":"2013","journal-title":"J Clin Invest"},{"issue":"1","key":"ref50","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/15548627.2015.1100356","article-title":"Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)","volume":"12","author":"DJ Klionsky","year":"2016","journal-title":"Autophagy"},{"issue":"3","key":"ref51","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.cell.2010.01.028","article-title":"Methods in mammalian autophagy research","volume":"140","author":"N Mizushima","year":"2010","journal-title":"Cell"},{"issue":"4","key":"ref52","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1038\/bjc.1997.412","article-title":"DDP-induced cytotoxicity is not influenced by p53 in nine human ovarian cancer cell lines with different p53 status","volume":"76","author":"P De Feudis","year":"1997","journal-title":"Br J Cancer"},{"issue":"2","key":"ref53","doi-asserted-by":"crossref","first-page":"278","DOI":"10.4161\/cc.23054","article-title":"Wild-type and mutant p53 mediate cisplatin resistance through interaction and inhibition of active caspase-9","volume":"12","author":"JL Chee","year":"2013","journal-title":"Cell Cycle"},{"issue":"4","key":"ref54","doi-asserted-by":"crossref","first-page":"225","DOI":"10.12717\/DR.2014.18.4.225","article-title":"Biphasic activity of chloroquine in human colorectal cancer cells","volume":"18","author":"D Park","year":"2014","journal-title":"Dev Reprod"},{"issue":"3","key":"ref55","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/S0163-7258(99)00073-X","article-title":"Resistance mechanisms associated with altered intracellular distribution of anticancer agents","volume":"85","author":"AK Larsen","year":"2000","journal-title":"Pharmacol Ther"},{"issue":"10","key":"ref56","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1084\/jem.20021952","article-title":"Lysosomal membrane permeabilization induces cell death in a mitochondrion-dependent fashion","volume":"197","author":"P Boya","year":"2003","journal-title":"J Exp Med"},{"issue":"4","key":"ref57","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.3892\/ol.2013.1154","article-title":"Effect of autophagy inhibition on chemotherapy-induced apoptosis in A549 lung cancer cells","volume":"5","author":"F Liu","year":"2013","journal-title":"Oncol Lett"},{"issue":"14","key":"ref58","doi-asserted-by":"crossref","first-page":"10850","DOI":"10.1074\/jbc.M109.080796","article-title":"Dual role of 3-methyladenine in modulation of autophagy via different temporal patterns of inhibition on class I and III phosphoinositide 3-kinase","volume":"285","author":"YT Wu","year":"2010","journal-title":"J Biol Chem"},{"issue":"10","key":"ref59","doi-asserted-by":"crossref","first-page":"3248","DOI":"10.1158\/1078-0432.CCR-10-0890","article-title":"Targeting autophagy augments in vitro and in vivo antimyeloma activity of DNA-damaging chemotherapy","volume":"17","author":"Y Pan","year":"2011","journal-title":"Clin Cancer Res"}],"updated-by":[{"DOI":"10.1371\/journal.pone.0197016","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2018,5,2]],"date-time":"2018-05-02T00:00:00Z","timestamp":1525219200000}}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0184922","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,18]],"date-time":"2020-05-18T08:27:06Z","timestamp":1589790426000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0184922"}},"subtitle":[],"editor":[{"given":"Vladimir","family":"Trajkovic","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2017,9,25]]},"references-count":59,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2017,9,25]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0184922","relation":{"correction":[{"id-type":"doi","id":"10.1371\/journal.pone.0197016","asserted-by":"object"}]},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,9,25]]}}}