{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T18:31:39Z","timestamp":1790015499360,"version":"4.0.1"},"reference-count":46,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T00:00:00Z","timestamp":1625097600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T00:00:00Z","timestamp":1625097600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T00:00:00Z","timestamp":1625097600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T00:00:00Z","timestamp":1625097600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T00:00:00Z","timestamp":1625097600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T00:00:00Z","timestamp":1625097600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T00:00:00Z","timestamp":1625097600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100002383","name":"King Saud University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002383","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Phytomedicine"],"published-print":{"date-parts":[[2021,7]]},"DOI":"10.1016\/j.phymed.2021.153574","type":"journal-article","created":{"date-parts":[[2021,4,16]],"date-time":"2021-04-16T04:20:20Z","timestamp":1618546820000},"page":"153574","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":17,"special_numbering":"C","title":["Blockage of the JAK\/STAT3 signaling pathway in multiple myeloma by leelamine"],"prefix":"10.1016","volume":"87","author":[{"given":"Young Yun","family":"Jung","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae-Young","family":"Um","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omaima","family":"Nasif","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sulaiman Ali","family":"Alharbi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gautam","family":"Sethi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2882-0612","authenticated-orcid":false,"given":"Kwang Seok","family":"Ahn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.phymed.2021.153574_bib0001","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1196\/annals.1378.063","article-title":"Targeting signal-transducer-and-activator-of-transcription-3 for prevention and therapy of cancer: modern target but ancient solution","volume":"1091","author":"Aggarwal","year":"2006","journal-title":"Ann N Y Acad Sci"},{"key":"10.1016\/j.phymed.2021.153574_bib0002","doi-asserted-by":"crossref","first-page":"4406","DOI":"10.1158\/0008-5472.CAN-07-6696","article-title":"Guggulsterone, a farnesoid X receptor antagonist, inhibits constitutive and inducible STAT3 activation through induction of a protein tyrosine phosphatase SHP-1","volume":"68","author":"Ahn","year":"2008","journal-title":"Cancer Res"},{"key":"10.1016\/j.phymed.2021.153574_bib0003","first-page":"10","article-title":"The Role of Signal Transducer and Activator of Transcription 3 (STAT3) and Its Targeted Inhibition in Hematological Malignancies","author":"Arora","year":"2018","journal-title":"Cancers (Basel)"},{"key":"10.1016\/j.phymed.2021.153574_bib0004","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1002\/jcp.25426","article-title":"Ginkgolic Acid Inhibits Invasion and Migration and TGF-beta-Induced EMT of Lung Cancer Cells Through PI3K\/Akt\/mTOR Inactivation","volume":"232","author":"Baek","year":"2017","journal-title":"J Cell Physiol"},{"key":"10.1016\/j.phymed.2021.153574_bib0005","doi-asserted-by":"crossref","DOI":"10.3390\/molecules22020276","article-title":"Ginkgolic Acid C 17:1, Derived from Ginkgo biloba Leaves, Suppresses Constitutive and Inducible STAT3 Activation through Induction of PTEN and SHP-1 Tyrosine Phosphatase","volume":"22","author":"Baek","year":"2017","journal-title":"Molecules"},{"key":"10.1016\/j.phymed.2021.153574_bib0006","doi-asserted-by":"crossref","first-page":"2657","DOI":"10.1093\/annonc\/mdt301","article-title":"Cancer mortality in Europe, 2005-2009, and an overview of trends since 1980","volume":"24","author":"Bosetti","year":"2013","journal-title":"Ann Oncol"},{"key":"10.1016\/j.phymed.2021.153574_bib0007","first-page":"945","article-title":"Activated STAT signaling in human tumors provides novel molecular targets for therapeutic intervention","volume":"8","author":"Buettner","year":"2002","journal-title":"Clin Cancer Res"},{"key":"10.1016\/j.phymed.2021.153574_bib0008","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/BJ20141337","article-title":"Analysis of the intricate relationship between chronic inflammation and cancer","volume":"468","author":"Chai","year":"2015","journal-title":"Biochem J"},{"issue":"Pt 1","key":"10.1016\/j.phymed.2021.153574_bib0009","first-page":"1","article-title":"Caspases: the executioners of apoptosis","volume":"326","author":"Cohen","year":"1997","journal-title":"Biochem J"},{"key":"10.1016\/j.phymed.2021.153574_bib0010","doi-asserted-by":"crossref","first-page":"12831","DOI":"10.18632\/oncotarget.14606","article-title":"A novel benzimidazole derivative, MBIC inhibits tumor growth and promotes apoptosis via activation of ROS-dependent JNK signaling pathway in hepatocellular carcinoma","volume":"8","author":"Dai","year":"2017","journal-title":"Oncotarget"},{"key":"10.1016\/j.phymed.2021.153574_bib0011","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":"Fulda","year":"2006","journal-title":"Oncogene"},{"key":"10.1016\/j.phymed.2021.153574_bib0012","article-title":"The pleiotropic role of transcription factor STAT3 in oncogenesis and its targeting through natural products for cancer prevention and therapy","author":"Garg","year":"2020","journal-title":"Med Res Rev"},{"key":"10.1016\/j.phymed.2021.153574_bib0013","doi-asserted-by":"crossref","first-page":"28260","DOI":"10.18632\/oncotarget.16002","article-title":"Identifying the structure-activity relationship of leelamine necessary for inhibiting intracellular cholesterol transport","volume":"8","author":"Gowda","year":"2017","journal-title":"Oncotarget"},{"key":"10.1016\/j.phymed.2021.153574_bib0014","first-page":"7","article-title":"Cancer statistics, 2000","volume":"50","author":"Greenlee","year":"2000","journal-title":"CA Cancer J Clin"},{"key":"10.1016\/j.phymed.2021.153574_bib0015","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.canlet.2011.04.015","article-title":"Embelin suppresses STAT3 signaling, proliferation, and survival of multiple myeloma via the protein tyrosine phosphatase PTEN","volume":"308","author":"Heo","year":"2011","journal-title":"Cancer Lett"},{"key":"10.1016\/j.phymed.2021.153574_bib0016","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1002\/stem.1609","article-title":"STAT3 phosphorylation at tyrosine 705 and serine 727 differentially regulates mouse ESC fates","volume":"32","author":"Huang","year":"2014","journal-title":"Stem Cells"},{"key":"10.1016\/j.phymed.2021.153574_bib0017","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/S0092-8674(00)81277-5","article-title":"STATs: signal transducers and activators of transcription","volume":"84","author":"Ihle","year":"1996","journal-title":"Cell"},{"key":"10.1016\/j.phymed.2021.153574_bib0018","doi-asserted-by":"crossref","first-page":"531","DOI":"10.3389\/fphar.2018.00531","article-title":"Anti-myeloma Effects of Icariin Are Mediated Through the Attenuation of JAK\/STAT3-Dependent Signaling Cascade","volume":"9","author":"Jung","year":"2018","journal-title":"Front Pharmacol"},{"key":"10.1016\/j.phymed.2021.153574_bib0019","doi-asserted-by":"crossref","DOI":"10.3390\/molecules24173127","article-title":"Fangchinoline, a Bisbenzylisoquinoline Alkaloid can Modulate Cytokine-Impelled Apoptosis via the Dual Regulation of NF-kappaB and AP-1 Pathways","volume":"24","author":"Jung","year":"2019","journal-title":"Molecules"},{"key":"10.1016\/j.phymed.2021.153574_bib0020","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1007\/s11055-008-0046-7","article-title":"Morphological characteristics of apoptosis and its significance in neurogenesis","volume":"38","author":"Kalinichenko","year":"2008","journal-title":"Neurosci Behav Physiol"},{"key":"10.1016\/j.phymed.2021.153574_bib0021","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1002\/mc.22035","article-title":"beta-Caryophyllene oxide inhibits constitutive and inducible STAT3 signaling pathway through induction of the SHP-1 protein tyrosine phosphatase","volume":"53","author":"Kim","year":"2014","journal-title":"Mol Carcinog"},{"key":"10.1016\/j.phymed.2021.153574_bib0022","doi-asserted-by":"crossref","DOI":"10.3390\/biom9070262","article-title":"Formononetin Regulates Multiple Oncogenic Signaling Cascades and Enhances Sensitivity to Bortezomib in a Multiple Myeloma Mouse Model","volume":"9","author":"Kim","year":"2019","journal-title":"Biomolecules"},{"key":"10.1016\/j.phymed.2021.153574_bib0023","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.canlet.2018.05.038","article-title":"Formononetin-induced oxidative stress abrogates the activation of STAT3\/5 signaling axis and suppresses the tumor growth in multiple myeloma preclinical model","volume":"431","author":"Kim","year":"2018","journal-title":"Cancer Lett"},{"key":"10.1016\/j.phymed.2021.153574_bib0024","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.canlet.2014.08.002","article-title":"Bergamottin, a natural furanocoumarin obtained from grapefruit juice induces chemosensitization and apoptosis through the inhibition of STAT3 signaling pathway in tumor cells","volume":"354","author":"Kim","year":"2014","journal-title":"Cancer Lett"},{"key":"10.1016\/j.phymed.2021.153574_bib0025","doi-asserted-by":"crossref","first-page":"4459","DOI":"10.1007\/s00018-020-03536-5","article-title":"The multifaceted role of reactive oxygen species in tumorigenesis","volume":"77","author":"Kirtonia","year":"2020","journal-title":"Cell Mol Life Sci"},{"key":"10.1016\/j.phymed.2021.153574_bib0026","doi-asserted-by":"crossref","first-page":"1690","DOI":"10.1158\/1535-7163.MCT-13-0868","article-title":"Leelamine mediates cancer cell death through inhibition of intracellular cholesterol transport","volume":"13","author":"Kuzu","year":"2014","journal-title":"Mol Cancer Ther"},{"key":"10.1016\/j.phymed.2021.153574_bib0028","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.canlet.2015.02.024","article-title":"Farnesol inhibits tumor growth and enhances the anticancer effects of bortezomib in multiple myeloma xenograft mouse model through the modulation of STAT3 signaling pathway","volume":"360","author":"Lee","year":"2015","journal-title":"Cancer Lett"},{"key":"10.1016\/j.phymed.2021.153574_bib0029","doi-asserted-by":"crossref","first-page":"6386","DOI":"10.18632\/oncotarget.3443","article-title":"Brassinin inhibits STAT3 signaling pathway through modulation of PIAS-3 and SOCS-3 expression and sensitizes human lung cancer xenograft in nude mice to paclitaxel","volume":"6","author":"Lee","year":"2015","journal-title":"Oncotarget"},{"key":"10.1016\/j.phymed.2021.153574_bib0030","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.biochi.2020.05.006","article-title":"Vitexin abrogates invasion and survival of hepatocellular carcinoma cells through targeting STAT3 signaling pathway","volume":"175","author":"Lee","year":"2020","journal-title":"Biochimie"},{"key":"10.1016\/j.phymed.2021.153574_bib0031","doi-asserted-by":"crossref","first-page":"216","DOI":"10.18632\/oncoscience.26","article-title":"Targeting constitutively-activated STAT3 in hypoxic ovarian cancer, using a novel STAT3 inhibitor","volume":"1","author":"McCann","year":"2014","journal-title":"Oncoscience"},{"key":"10.1016\/j.phymed.2021.153574_bib0032","doi-asserted-by":"crossref","DOI":"10.3390\/biomedicines7030053","article-title":"A Brief Overview of the Antitumoral Actions of Leelamine","volume":"7","author":"Merarchi","year":"2019","journal-title":"Biomedicines"},{"key":"10.1016\/j.phymed.2021.153574_bib0033","doi-asserted-by":"crossref","first-page":"34296","DOI":"10.1074\/jbc.M114.601104","article-title":"Development of a novel azaspirane that targets the Janus kinase-signal transducer and activator of transcription (STAT) pathway in hepatocellular carcinoma in vitro and in vivo","volume":"289","author":"Mohan","year":"2014","journal-title":"J Biol Chem"},{"key":"10.1016\/j.phymed.2021.153574_bib0034","article-title":"Targeting STAT3 signaling pathway in cancer by agents derived from Mother Nature","author":"Mohan","year":"2020","journal-title":"Semin Cancer Biol"},{"key":"10.1016\/j.phymed.2021.153574_bib0035","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1182\/blood-2014-10-609461","article-title":"Future distribution of multiple myeloma in the United States by sex, age, and race\/ethnicity","volume":"125","author":"Rosenberg","year":"2015","journal-title":"Blood"},{"key":"10.1016\/j.phymed.2021.153574_bib0036","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1002\/mc.22497","article-title":"Cancer-selective death of human breast cancer cells by leelamine is mediated by bax and bak activation","volume":"56","author":"Sehrawat","year":"2017","journal-title":"Mol Carcinog"},{"key":"10.1016\/j.phymed.2021.153574_bib0037","doi-asserted-by":"crossref","first-page":"365","DOI":"10.3389\/fphar.2018.00365","article-title":"Celastrol Attenuates the Invasion and Migration and Augments the Anticancer Effects of Bortezomib in a Xenograft Mouse Model of Multiple Myeloma","volume":"9","author":"Shanmugam","year":"2018","journal-title":"Front Pharmacol"},{"key":"10.1016\/j.phymed.2021.153574_bib0038","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.semcancer.2016.03.005","article-title":"Cancer prevention and therapy through the modulation of transcription factors by bioactive natural compounds","volume":"40-41","author":"Shanmugam","year":"2016","journal-title":"Semin Cancer Biol"},{"key":"10.1016\/j.phymed.2021.153574_bib0039","doi-asserted-by":"crossref","first-page":"2079","DOI":"10.1158\/1535-7163.MCT-18-0117","article-title":"Therapeutic Potential of Leelamine, a Novel Inhibitor of Androgen Receptor and Castration-Resistant Prostate Cancer","volume":"17","author":"Singh","year":"2018","journal-title":"Mol Cancer Ther"},{"key":"10.1016\/j.phymed.2021.153574_bib0040","first-page":"136","article-title":"Targeting the STAT3 signaling pathway in cancer: role of synthetic and natural inhibitors","volume":"1845","author":"Siveen","year":"2014","journal-title":"Biochim Biophys Acta"},{"key":"10.1016\/j.phymed.2021.153574_bib0041","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1007\/s10286-012-0164-8","article-title":"Bortezomib-induced severe autonomic neuropathy","volume":"22","author":"Stratogianni","year":"2012","journal-title":"Clin Auton Res"},{"key":"10.1016\/j.phymed.2021.153574_bib0042","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.transci.2013.07.017","article-title":"Continuous treatment in multiple myeloma: the future?","volume":"49","author":"Vande Broek","year":"2013","journal-title":"Transfus Apher Sci"},{"key":"10.1016\/j.phymed.2021.153574_bib0043","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1016\/j.gastrohep.2012.05.007","article-title":"Thalidomide-induced acute cholestatic hepatitis: case report and review of the literature","volume":"35","author":"Vilas-Boas","year":"2012","journal-title":"Gastroenterol Hepatol"},{"key":"10.1016\/j.phymed.2021.153574_bib0044","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1080\/13543784.2017.1351941","article-title":"Do STAT3 inhibitors have potential in the future for cancer therapy?","volume":"26","author":"Wong","year":"2017","journal-title":"Expert Opin Investig Drugs"},{"key":"10.1016\/j.phymed.2021.153574_bib0045","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1038\/nrc1275","article-title":"The STATs of cancer\u2013new molecular targets come of age","volume":"4","author":"Yu","year":"2004","journal-title":"Nat Rev Cancer"},{"key":"10.1016\/j.phymed.2021.153574_bib0046","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1038\/nrc3818","article-title":"Revisiting STAT3 signalling in cancer: new and unexpected biological functions","volume":"14","author":"Yu","year":"2014","journal-title":"Nat Rev Cancer"},{"key":"10.1016\/j.phymed.2021.153574_bib0047","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1089\/ars.2015.6418","article-title":"Nimbolide-Induced Oxidative Stress Abrogates STAT3 Signaling Cascade and Inhibits Tumor Growth in Transgenic Adenocarcinoma of Mouse Prostate Model","volume":"24","author":"Zhang","year":"2016","journal-title":"Antioxid Redox Signal"}],"container-title":["Phytomedicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0944711321001161?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0944711321001161?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T18:28:05Z","timestamp":1760552885000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0944711321001161"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7]]},"references-count":46,"alternative-id":["S0944711321001161"],"URL":"https:\/\/doi.org\/10.1016\/j.phymed.2021.153574","relation":{},"ISSN":["0944-7113"],"issn-type":[{"value":"0944-7113","type":"print"}],"subject":[],"published":{"date-parts":[[2021,7]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Blockage of the JAK\/STAT3 signaling pathway in multiple myeloma by leelamine","name":"articletitle","label":"Article Title"},{"value":"Phytomedicine","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.phymed.2021.153574","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 Elsevier GmbH. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"153574"}}