{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T18:02:29Z","timestamp":1787594549906,"version":"build-2736575974"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81860477"],"award-info":[{"award-number":["81860477"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>To evaluate the inhibitory effect and mechanism of plumbagin (PLB) against drug-resistant tongue squamous cell carcinoma (TSCC), and whether its antitumour effect is not affected by tumour drug resistance.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>TSCC sensitive CAL27 cells and drug-resistant CAL27\/RE cells were used to study the cytotoxicity and mechanism of PLB in vitro, including CCK-8 analysis, colony formation, DAPI staining, flow cytometry assay, transmission electron microscopy, western blotting assay, autophagy, apoptosis and ROS fluorescent probes. BALB\/c nude mice xenograft models were used to study the growth inhibitory effect of PLB in vivo.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Key findings<\/jats:title>\n                  <jats:p>The results showed that the cell viability and proliferation inhibition and apoptosis induction abilities of PLB on drug-resistant cells were more obvious than that on sensitive cells. And PLB induced protective autophagy in TSCC cells. Mechanistically, PLB induced apoptosis and autophagy by generating reactive oxygen species to mediate JNK and AKT\/mTOR pathways. Finally, the growth inhibitory effect of PLB against drug-resistant TSCC was also confirmed in vivo.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>PLB will be a promising anticancer agent to overcome drug-resistant TSCC without being affected by its drug resistance properties.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jpp\/rgaa027","type":"journal-article","created":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T04:13:53Z","timestamp":1609474433000},"page":"98-109","source":"Crossref","is-referenced-by-count":15,"title":["Cytotoxicity mechanisms of plumbagin in drug-resistant tongue squamous cell carcinoma"],"prefix":"10.1093","volume":"73","author":[{"given":"Danfeng","family":"Xue","sequence":"first","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Nanchang University , Nanchang, Jiangxi,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiongming","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Nanchang University , Nanchang, Jiangxi,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4629-1785","authenticated-orcid":false,"given":"Jiaxuan","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Nanchang University , Nanchang, Jiangxi,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,1,1]]},"reference":[{"key":"2024103012051641500_CIT0001","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21442","article-title":"Cancer statistics, 2018","volume":"68","author":"Siegel","year":"2018","journal-title":"CA Cancer J Clin"},{"key":"2024103012051641500_CIT0002","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1158\/0008-5472.CAN-16-1322","article-title":"Circadian clock gene Bmal1 inhibits tumorigenesis and increases paclitaxel sensitivity in tongue squamous cell carcinoma","volume":"77","author":"Tang","year":"2017","journal-title":"Cancer Res"},{"key":"2024103012051641500_CIT0003","doi-asserted-by":"crossref","first-page":"445","DOI":"10.4103\/jispcd.JISPCD_394_18","article-title":"Temporomandibular disorder among women who experienced posttraumatic stress disorder after a miscarriage","volume":"9","author":"Abu-Raisi","year":"2019","journal-title":"J Int Soc Prev Community Dent"},{"key":"2024103012051641500_CIT0004","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.oraloncology.2017.02.015","article-title":"MicroRNAs in human tongue squamous cell carcinoma: From pathogenesis to therapeutic implications","volume":"67","author":"Karatas","year":"2017","journal-title":"Oral Oncol"},{"key":"2024103012051641500_CIT0005","doi-asserted-by":"crossref","first-page":"87037","DOI":"10.18632\/oncotarget.13523","article-title":"CCL2\/EGF positive feedback loop between cancer cells and macrophages promotes cell migration and invasion in head and neck squamous cell carcinoma","volume":"7","author":"Gao","year":"2016","journal-title":"Oncotarget"},{"key":"2024103012051641500_CIT0006","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.3390\/cancers3011351","article-title":"Cisplatin as an anti-tumor drug: cellular mechanisms of activity, drug resistance and induced side effects","volume":"3","author":"Florea","year":"2011","journal-title":"Cancers (Basel)"},{"key":"2024103012051641500_CIT0007","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1016\/j.biopha.2018.12.010","article-title":"Phytochemicals: current strategy to sensitize cancer cells to cisplatin","volume":"110","author":"Sun","year":"2019","journal-title":"Biomed Pharmacother"},{"key":"2024103012051641500_CIT0008","doi-asserted-by":"crossref","first-page":"17023","DOI":"10.1074\/jbc.M601595200","article-title":"Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone) suppresses NF-kappaB activation and NF-kappaB-regulated gene products through modulation of p65 and IkappaBalpha kinase activation, leading to potentiation of apoptosis induced by cytokine and chemotherapeutic agents","volume":"281","author":"Sandur","year":"2006","journal-title":"J Biol Chem"},{"key":"2024103012051641500_CIT0009","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1016\/j.fct.2019.01.018","article-title":"Emerging role of plumbagin: cytotoxic potential and pharmaceutical relevance towards cancer therapy","volume":"125","author":"Tripathi","year":"2019","journal-title":"Food Chem Toxicol"},{"key":"2024103012051641500_CIT0010","first-page":"1601","article-title":"Plumbagin induces G2\/M arrest, apoptosis, and autophagy via p38 MAPK- and PI3K\/Akt\/mTOR-mediated pathways in human tongue squamous cell carcinoma cells","volume":"9","author":"Pan","year":"2015","journal-title":"Drug Des Devel Ther"},{"key":"2024103012051641500_CIT0011","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1111\/odi.12799","article-title":"Plumbagin-mediating GLUT1 suppresses the growth of human tongue squamous cell carcinoma","volume":"24","author":"Na","year":"2018","journal-title":"Oral Dis"},{"key":"2024103012051641500_CIT0012","doi-asserted-by":"crossref","first-page":"105732","DOI":"10.1016\/j.biocel.2020.105732","article-title":"ROS enhances the cytotoxicity of cisplatin by inducing apoptosis and autophagy in tongue squamous cell carcinoma cells","volume":"122","author":"Xue","year":"2020","journal-title":"Int J Biochem Cell Biol"},{"key":"2024103012051641500_CIT0013","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1038\/nrc3462","article-title":"Apoptosis: refined and lethal","volume":"13","author":"Burgess","year":"2013","journal-title":"Nat Rev Cancer"},{"key":"2024103012051641500_CIT0014","first-page":"2832","article-title":"SLFN5 influences proliferation and apoptosis by upregulating PTEN transcription via ZEB1 and inhibits the purine metabolic pathway in breast cancer","volume":"10","author":"Gu","year":"2020","journal-title":"Am J Cancer Res"},{"key":"2024103012051641500_CIT0015","doi-asserted-by":"crossref","first-page":"1758835920913432","DOI":"10.1177\/1758835920913432","article-title":"AR420626, a selective agonist of GPR41\/FFA3, suppresses growth of hepatocellular carcinoma cells by inducing apoptosis via HDAC inhibition","volume":"12","author":"Mikami","year":"2020","journal-title":"Ther Adv Med Oncol"},{"key":"2024103012051641500_CIT0016","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1080\/15548627.2017.1389356","article-title":"The Vici syndrome protein EPG5 regulates intracellular nucleic acid trafficking linking autophagy to innate and adaptive immunity","volume":"14","author":"Piano Mortari","year":"2018","journal-title":"Autophagy"},{"key":"2024103012051641500_CIT0017","doi-asserted-by":"crossref","DOI":"10.3390\/cancers11101599","article-title":"Targeting autophagy for cancer treatment and tumor chemosensitization","volume":"11","author":"P\u00e9rez-Hern\u00e1ndez","year":"2019","journal-title":"Cancers (Basel)"},{"key":"2024103012051641500_CIT0018","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.canlet.2016.03.042","article-title":"Reactive oxygen species (ROS) and cancer: role of antioxidative nutraceuticals","volume":"387","author":"Prasad","year":"2017","journal-title":"Cancer Lett"},{"key":"2024103012051641500_CIT0019","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1038\/nchembio.607","article-title":"Chemistry and biology of reactive oxygen species in signaling or stress responses","volume":"7","author":"Dickinson","year":"2011","journal-title":"Nat Chem Biol"},{"key":"2024103012051641500_CIT0020","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1101\/sqb.2016.81.030791","article-title":"Cancer, oxidative stress, and metastasis","volume":"81","author":"Gill","year":"2016","journal-title":"Cold Spring Harb Symp Quant Biol"},{"key":"2024103012051641500_CIT0021","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1016\/j.arr.2012.10.004","article-title":"Oxidative stress and cancer: an overview","volume":"12","author":"Sosa","year":"2013","journal-title":"Ageing Res Rev"},{"key":"2024103012051641500_CIT0022","doi-asserted-by":"crossref","DOI":"10.3390\/cancers11071003","article-title":"Identification of withaferin a as a potential candidate for anti-cancer therapy in non-small cell lung cancer","volume":"11","author":"Hsu","year":"2019","journal-title":"Cancers (Basel)"},{"key":"2024103012051641500_CIT0023","doi-asserted-by":"crossref","first-page":"9051542","DOI":"10.1155\/2019\/9051542","article-title":"ROS-mediated cancer cell killing through dietary phytochemicals","volume":"2019","author":"NavaneethaKrishnan","year":"2019","journal-title":"Oxid Med Cell Longev"},{"key":"2024103012051641500_CIT0024","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1007\/s12272-020-01221-6","article-title":"Plumbagin engenders apoptosis in lung cancer cells via caspase-9 activation and targeting mitochondrial-mediated ROS induction","volume":"43","author":"Tripathi","year":"2020","journal-title":"Arch Pharm Res"},{"key":"2024103012051641500_CIT0025","doi-asserted-by":"crossref","first-page":"5480","DOI":"10.3892\/mmr.2017.7222","article-title":"Plumbagin induces apoptosis in human osteosarcoma through ROS generation, endoplasmic reticulum stress and mitochondrial apoptosis pathway","volume":"16","author":"Chao","year":"2017","journal-title":"Mol Med Rep"},{"key":"2024103012051641500_CIT0026","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1016\/j.ejphar.2015.08.058","article-title":"The role of thioredoxin reductase and glutathione reductase in plumbagin-induced, reactive oxygen species-mediated apoptosis in cancer cell lines","volume":"765","author":"Hwang","year":"2015","journal-title":"Eur J Pharmacol"},{"key":"2024103012051641500_CIT0027","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1186\/s13046-018-0909-x","article-title":"The role of cellular reactive oxygen species in cancer chemotherapy","volume":"37","author":"Yang","year":"2018","journal-title":"J Exp Clin Cancer Res"},{"key":"2024103012051641500_CIT0028","article-title":"Redox-mediated mechanism of chemoresistance in cancer cells","volume":"8","author":"Kim","year":"2019","journal-title":"Antioxidants (Basel)"},{"key":"2024103012051641500_CIT0029","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1186\/s13046-019-1173-4","article-title":"Celastrol mediates autophagy and apoptosis via the ROS\/JNK and Akt\/mTOR signaling pathways in glioma cells","volume":"38","author":"Liu","year":"2019","journal-title":"J Exp Clin Cancer Res"},{"key":"2024103012051641500_CIT0030","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.freeradbiomed.2017.02.015","article-title":"Arsenic sulfide induces apoptosis and autophagy through the activation of ROS\/JNK and suppression of Akt\/mTOR signaling pathways in osteosarcoma","volume":"106","author":"Wang","year":"2017","journal-title":"Free Radic Biol Med"},{"key":"2024103012051641500_CIT0031","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.redox.2014.09.004","article-title":"Regulation of the effects of CYP2E1-induced oxidative stress by JNK signaling","volume":"3","author":"Schattenberg","year":"2014","journal-title":"Redox Biol"},{"key":"2024103012051641500_CIT0032","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1159\/000486773","article-title":"Plumbagin triggers ER stress-mediated apoptosis in prostate cancer cells via induction of ROS","volume":"45","author":"Huang","year":"2018","journal-title":"Cell Physiol Biochem"},{"key":"2024103012051641500_CIT0033","doi-asserted-by":"crossref","first-page":"104517","DOI":"10.1016\/j.phrs.2019.104517","article-title":"Plumbagin inhibits cancer stem-like cells, angiogenesis and suppresses cell proliferation and invasion by targeting Wnt\/\u03b2-catenin pathway in endocrine resistant breast cancer","volume":"150","author":"Sakunrangsit","year":"2019","journal-title":"Pharmacol Res"},{"key":"2024103012051641500_CIT0034","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/j.intimp.2017.12.021","article-title":"Plumbagin suppresses the human large cell lung cancer cell lines by inhibiting IL-6\/STAT3 signaling in vitro","volume":"55","author":"Yu","year":"2018","journal-title":"Int Immunopharmacol"},{"key":"2024103012051641500_CIT0035","doi-asserted-by":"crossref","first-page":"716","DOI":"10.3109\/07388551.2015.1015957","article-title":"Molecular mechanisms of drug resistance and its reversal in cancer","volume":"36","author":"Kartal-Yandim","year":"2016","journal-title":"Crit Rev Biotechnol"},{"key":"2024103012051641500_CIT0036","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1038\/s41419-020-2658-y","article-title":"Mitochondrial dysfunction generates aggregates that resist lysosomal degradation in human breast cancer cells","volume":"11","author":"Biel","year":"2020","journal-title":"Cell Death Dis"},{"key":"2024103012051641500_CIT0037","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1038\/s41419-020-2390-7","article-title":"MicroRNA-30a targets BECLIN-1 to inactivate autophagy and sensitizes gastrointestinal stromal tumor cells to imatinib","volume":"11","author":"Chen","year":"2020","journal-title":"Cell Death Dis"},{"key":"2024103012051641500_CIT0038","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1186\/s40880-017-0219-2","article-title":"Autophagy and multidrug resistance in cancer","volume":"36","author":"Li","year":"2017","journal-title":"Chin J Cancer"},{"key":"2024103012051641500_CIT0039","article-title":"Molecular mechanisms underlying autophagy-mediated treatment resistance in cancer","volume":"11: 1775","author":"Ho","year":"2019","journal-title":"Cancers (Basel)"},{"key":"2024103012051641500_CIT0040","doi-asserted-by":"crossref","first-page":"260","DOI":"10.3390\/diseases3040260","article-title":"Synergistic anticancer activities of natural substances in human hepatocellular carcinoma","volume":"3","author":"Kojima-Yuasa","year":"2015","journal-title":"Diseases"},{"key":"2024103012051641500_CIT0041","doi-asserted-by":"crossref","DOI":"10.3390\/biom10020345","article-title":"Antiproliferative effect of acridine chalcone is mediated by induction of oxidative stress","volume":"10","author":"Takac","year":"2020","journal-title":"Biomolecules"},{"key":"2024103012051641500_CIT0042","doi-asserted-by":"crossref","first-page":"111253","DOI":"10.1016\/j.fct.2020.111253","article-title":"Thymoquinone induces apoptosis of human renal carcinoma Caki-1 cells by inhibiting JAK2\/STAT3 through pro-oxidant effect","volume":"139","author":"Chae","year":"2020","journal-title":"Food Chem Toxicol"},{"key":"2024103012051641500_CIT0043","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1186\/s13046-018-0922-0","article-title":"Synergistic inhibitory effects of capsaicin combined with cisplatin on human osteosarcoma in culture and in xenografts","volume":"37","author":"Wang","year":"2018","journal-title":"J Exp Clin Cancer Res"},{"key":"2024103012051641500_CIT0044","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1186\/s13046-019-1215-y","article-title":"Curcuminoid WZ35 synergize with cisplatin by inducing ROS production and inhibiting TrxR1 activity in gastric cancer cells","volume":"38","author":"He","year":"2019","journal-title":"J Exp Clin Cancer Res"},{"key":"2024103012051641500_CIT0045","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.cbi.2017.08.011","article-title":"Colistin-induced autophagy and apoptosis involves the JNK-Bcl2-Bax signaling pathway and JNK-p53-ROS positive feedback loop in PC-12 cells","volume":"277","author":"Lu","year":"2017","journal-title":"Chem Biol Interact"},{"key":"2024103012051641500_CIT0046","first-page":"280","article-title":"Inactivated sendai virus induces ROS-dependent apoptosis and autophagy in human prostate cancer cells","volume":"31","author":"Qian","year":"2018","journal-title":"Biomed Environ Sci"},{"key":"2024103012051641500_CIT0047","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1186\/s13046-020-01621-y","article-title":"Mitochondrial ROS accumulation inhibiting JAK2\/STAT3 pathway is a critical modulator of CYT997-induced autophagy and apoptosis in gastric cancer","volume":"39","author":"Cao","year":"2020","journal-title":"J Exp Clin Cancer Res"},{"key":"2024103012051641500_CIT0048","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1038\/s41419-020-2317-3","article-title":"Bruceine D induces lung cancer cell apoptosis and autophagy via the ROS\/MAPK signaling pathway in vitro and in vivo","volume":"11","author":"Fan","year":"2020","journal-title":"Cell Death Dis"},{"key":"2024103012051641500_CIT0049","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.bcp.2019.07.008","article-title":"Ginsenoside Rg5 induces G2\/M phase arrest, apoptosis and autophagy via regulating ROS-mediated MAPK pathways against human gastric cancer","volume":"168","author":"Liu","year":"2019","journal-title":"Biochem Pharmacol"},{"key":"2024103012051641500_CIT0050","first-page":"2580","article-title":"Anemoside B4 exerts anti-cancer effect by inducing apoptosis and autophagy through inhibiton of PI3K\/Akt\/mTOR pathway in hepatocellular carcinoma","volume":"11","author":"Xue","year":"2019","journal-title":"Am J Transl Res"},{"key":"2024103012051641500_CIT0051","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1038\/s41419-020-2602-1","article-title":"Molecular mechanisms of methylglyoxal-induced aortic endothelial dysfunction in human vascular endothelial cells","volume":"11","author":"Lee","year":"2020","journal-title":"Cell Death Dis"}],"container-title":["Journal of Pharmacy and Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jpp\/article-pdf\/73\/1\/98\/60216678\/rgaa027.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jpp\/article-pdf\/73\/1\/98\/60216678\/rgaa027.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T16:42:25Z","timestamp":1730306545000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jpp\/article\/73\/1\/98\/6027734"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,1]]},"references-count":51,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,1,1]]},"published-print":{"date-parts":[[2021,1,1]]}},"URL":"https:\/\/doi.org\/10.1093\/jpp\/rgaa027","relation":{},"ISSN":["0022-3573","2042-7158"],"issn-type":[{"value":"0022-3573","type":"print"},{"value":"2042-7158","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,1,1]]},"published":{"date-parts":[[2021,1,1]]}}}