{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T17:00:28Z","timestamp":1793293228058,"version":"4.5.0"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2021,11,9]],"date-time":"2021-11-09T00:00:00Z","timestamp":1636416000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,11,9]],"date-time":"2021-11-09T00:00:00Z","timestamp":1636416000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100012247","name":"program of shanghai academic research leader","doi-asserted-by":"publisher","award":["18ZR1412900"],"award-info":[{"award-number":["18ZR1412900"]}],"id":[{"id":"10.13039\/501100012247","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cogn Neurodyn"],"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The high mortality rate of non-small-cell lung cancer (NSCLC) is mostly due to the high risk of recurrence. A comprehensive understanding of proliferation mechanisms of NSCLC would remarkably contribute to blocking up the invasion and metastasis of tumor cells. In our previous study, the remarkable decreased activity of Thiamine-dependent enzymes (TDEs), involving in intermediary metabolism responsible for energy production of tumor, was found under conditions of thiamine deficiency in vivo. To explore the effect of Oxythiamine (OT), a TDEs antimetabolite, on cell growth, we co-cultured A549 cells with OT in vitro at various doses (0.1, 1, 10 and 100\u00a0\u03bcM) and time periods (6, 12, 24 and 48\u00a0h) and subsequent cell proliferation and apoptosis assays were performed respectively. Our findings demonstrated that A549 cells proliferation was significantly downregulated by OT treatment in a progressively dose as well as time dependent manner. Inhibition of TDEs resulted in antagonism of lung cancer growth by inducing cells to cease the cycle as well as apoptotic cell death. We concluded a critical role of OT, a TDEs antagonistic compound, indicating the potential target of its practical use.<\/jats:p>","DOI":"10.1007\/s11571-021-09725-7","type":"journal-article","created":{"date-parts":[[2021,11,9]],"date-time":"2021-11-09T05:06:00Z","timestamp":1636434360000},"page":"633-641","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A dose- and time-dependent effect of oxythiamine on cell growth inhibition in non-small cell lung cancer"],"prefix":"10.1007","volume":"16","author":[{"given":"Lin","family":"Bai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui-li","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,11,9]]},"reference":[{"issue":"5","key":"9725_CR1","doi-asserted-by":"publisher","first-page":"1191","DOI":"10.1007\/s00345-012-0874-5","volume":"31","author":"D Baumunk","year":"2013","unstructured":"Baumunk D, Reichelt U, Hildebrandt J, Krause H, Ebbing J, Cash H, Miller K, Schostak M, Weikert S (2013) Expression parameters of the metabolic pathway genes pyruvate dehydrogenase kinase-1 (PDK-1) and DJ-1\/PARK7 in renal cell carcinoma (RCC). World J Urol 31(5):1191\u20131196. https:\/\/doi.org\/10.1007\/s00345-012-0874-5","journal-title":"World J Urol"},{"issue":"6","key":"9725_CR2","doi-asserted-by":"publisher","first-page":"962","DOI":"10.1038\/cdd.2016.11","volume":"23","author":"RB Birge","year":"2016","unstructured":"Birge RB, Boeltz S, Kumar S, Carlson J, Wanderley J, Calianese D, Barcinski M, Brekken RA, Huang X, Hutchins JT, Freimark B, Empig C, Mercer J, Schroit AJ, Schett G, Herrmann M (2016) Phosphatidylserine is a global immunosuppressive signal in efferocytosis, infectious disease, and cancer. Cell Death Differ 23(6):962\u2013978. https:\/\/doi.org\/10.1038\/cdd.2016.11","journal-title":"Cell Death Differ"},{"issue":"5","key":"9725_CR3","first-page":"1183","volume":"60","author":"LG Boros","year":"2000","unstructured":"Boros LG, Torday JS, Lim S, Bassilian S, Cascante M, Lee WN (2000) Transforming growth factor beta2 promotes glucose carbon incorporation into nucleic acid ribose through the nonoxidative pentose cycle in lung epithelial carcinoma cells. Can Res 60(5):1183\u20131185","journal-title":"Can Res"},{"issue":"2","key":"9725_CR4","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1038\/nrc2981","volume":"1","author":"RA Cairns","year":"2011","unstructured":"Cairns RA, Harris IS, Mak TW (2011) Regulation of cancer cell metabolism. Nat Rev Cancer 1(2):85\u201395","journal-title":"Nat Rev Cancer"},{"key":"9725_CR5","doi-asserted-by":"publisher","first-page":"13892","DOI":"10.1038\/ncomms13892","volume":"8","author":"A Chauvier","year":"2017","unstructured":"Chauvier A, Picard-Jean F, Berger-Dancause JC, Bastet L, Naghdi MR, Dub\u00e9 A, Turcotte P, Perreault J, Lafontaine DA (2017) Transcriptional pausing at the translation start site operates as a critical checkpoint for riboswitch regulation. Nat Commun 8:13892. https:\/\/doi.org\/10.1038\/ncomms13892","journal-title":"Nat Commun"},{"issue":"2","key":"9725_CR6","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1007\/s12094-015-1352-5","volume":"18","author":"M Grimm","year":"2016","unstructured":"Grimm M, Calg\u00e9er B, Teriete P, Biegner T, Munz A, Reinert S (2016) Targeting thiamine-dependent enzymes for metabolic therapies in oral squamous cell carcinoma? Clin Transl Oncol off Publ Fed Span Oncol Soc Natl Cancer Inst Mexico 18(2):196\u2013205. https:\/\/doi.org\/10.1007\/s12094-015-1352-5","journal-title":"Clin Transl Oncol off Publ Fed Span Oncol Soc Natl Cancer Inst Mexico"},{"key":"9725_CR7","doi-asserted-by":"publisher","first-page":"850","DOI":"10.1016\/j.bios.2016.09.049","volume":"87","author":"M Halma","year":"2017","unstructured":"Halma M, Doum\u00e8che B, Hecquet L, Pr\u00e9vot V, Mousty C, Charmantray F (2017) Thiamine biosensor based on oxidative trapping of enzyme-substrate intermediate. Biosens Bioelectron 87:850\u2013857. https:\/\/doi.org\/10.1016\/j.bios.2016.09.049","journal-title":"Biosens Bioelectron"},{"issue":"7","key":"9725_CR8","doi-asserted-by":"publisher","first-page":"640","DOI":"10.1056\/NEJMoa1916623","volume":"383","author":"N Howlader","year":"2020","unstructured":"Howlader N, Forjaz G, Mooradian MJ, Meza R, Kong CY, Cronin KA, Mariotto AB, Lowy DR, Feuer EJ (2020) The effect of advances in lung-cancer treatment on population mortality. N Engl J Med 383(7):640\u2013649. https:\/\/doi.org\/10.1056\/NEJMoa1916623","journal-title":"N Engl J Med"},{"issue":"1","key":"9725_CR9","doi-asserted-by":"publisher","first-page":"44","DOI":"10.3892\/ijo.2012.1687","volume":"42","author":"H Hur","year":"2013","unstructured":"Hur H, Xuan Y, Kim YB, Lee G, Shim W, Yun J, Ham IH, Han SU (2013) Expression of pyruvate dehydrogenase kinase-1 in gastric cancer as a potential therapeutic target. Int J Oncol 42(1):44\u201354. https:\/\/doi.org\/10.3892\/ijo.2012.1687","journal-title":"Int J Oncol"},{"issue":"3","key":"9725_CR10","doi-asserted-by":"publisher","first-page":"1156","DOI":"10.1158\/0008-5472.CAN-10-0717","volume":"71","author":"XD Ji","year":"2011","unstructured":"Ji XD, Li G, Feng YX, Zhao JS, Li JJ, Sun ZJ, Shi S, Deng YZ, Xu JF, Zhu YQ, Koeffler HP, Tong XJ, Xie D (2011) EphB3 is overexpressed in non-small-cell lung cancer and promotes tumor metastasis by enhancing cell survival and migration. Can Res 71(3):1156\u20131166. https:\/\/doi.org\/10.1158\/0008-5472.CAN-10-0717","journal-title":"Can Res"},{"issue":"6","key":"9725_CR11","doi-asserted-by":"publisher","first-page":"1453","DOI":"10.1183\/09031936.00015710","volume":"37","author":"CC Lin","year":"2011","unstructured":"Lin CC, Chen LC, Tseng VS, Yan JJ, Lai WW, Su WP, Lin CH, Huang CY, Su WC (2011) Malignant pleural effusion cells show aberrant glucose metabolism gene expression. Eur Respir J 37(6):1453\u20131465. https:\/\/doi.org\/10.1183\/09031936.00015710","journal-title":"Eur Respir J"},{"issue":"15","key":"9725_CR12","doi-asserted-by":"publisher","first-page":"6368","DOI":"10.1158\/0008-5472.CAN-09-4615","volume":"70","author":"H Liu","year":"2010","unstructured":"Liu H, Huang D, McArthur DL, Boros LG, Nissen N, Heaney AP (2010) Fructose induces transketolase flux to promote pancreatic cancer growth. Can Res 70(15):6368\u20136376. https:\/\/doi.org\/10.1158\/0008-5472.CAN-09-4615","journal-title":"Can Res"},{"key":"9725_CR13","doi-asserted-by":"publisher","first-page":"110595","DOI":"10.1016\/j.mce.2019.110595","volume":"499","author":"CL Liu","year":"2020","unstructured":"Liu CL, Hsu YC, Lee JJ, Chen MJ, Lin CH, Huang SY, Cheng SP (2020) Targeting the pentose phosphate pathway increases reactive oxygen species and induces apoptosis in thyroid cancer cells. Mol Cell Endocrinol 499:110595. https:\/\/doi.org\/10.1016\/j.mce.2019.110595","journal-title":"Mol Cell Endocrinol"},{"issue":"3","key":"9725_CR14","doi-asserted-by":"publisher","first-page":"1405","DOI":"10.1016\/j.ajpath.2011.05.050","volume":"179","author":"CW Lu","year":"2011","unstructured":"Lu CW, Lin SC, Chien CW, Lin SC, Lee CT, Lin BW, Lee JC, Tsai SJ (2011) Overexpression of pyruvate dehydrogenase kinase 3 increases drug resistance and early recurrence in colon cancer. Am J Pathol 179(3):1405\u20131414. https:\/\/doi.org\/10.1016\/j.ajpath.2011.05.050","journal-title":"Am J Pathol"},{"issue":"3","key":"9725_CR15","doi-asserted-by":"publisher","first-page":"11043","DOI":"10.4238\/2015.September.21.17","volume":"14","author":"H Lu","year":"2015","unstructured":"Lu H, Lan WX, Bo L, Niu C, Zhou JJ, Zhu HL (2015) Metabolic response of LLC xenografted mice to oxythiamine, as measured by [1H] NMR spectroscopy. Genet Mol Res GMR 14(3):11043\u201311051. https:\/\/doi.org\/10.4238\/2015.September.21.17","journal-title":"Genet Mol Res GMR"},{"issue":"3","key":"9725_CR16","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1002\/ana.24998","volume":"82","author":"JD Ortigoza-Escobar","year":"2017","unstructured":"Ortigoza-Escobar JD, Alfadhel M, Molero-Luis M, Darin N, Spiegel R, De Coo IF, Gerards M, Taylor RW, Artuch R, Nashabat M, Rodr\u00edguez-Pombo P, Tabarki B, P\u00e9rez-Due\u00f1as B, Thiamine Deficiency Study Group (2017) Thiamine deficiency in childhood with attention to genetic causes: survival and outcome predictors. Ann Neurol 82(3):317\u2013330. https:\/\/doi.org\/10.1002\/ana.24998","journal-title":"Ann Neurol"},{"issue":"11","key":"9725_CR17","doi-asserted-by":"publisher","first-page":"3380","DOI":"10.3390\/nu12113380","volume":"12","author":"CT Peterson","year":"2020","unstructured":"Peterson CT, Rodionov DA, Osterman AL, Peterson SN (2020) B vitamins and their role in immune regulation and cancer. Nutrients 12(11):3380. https:\/\/doi.org\/10.3390\/nu12113380","journal-title":"Nutrients"},{"issue":"7","key":"9725_CR18","doi-asserted-by":"publisher","first-page":"706","DOI":"10.1046\/j.1440-1746.2000.02205.x","volume":"15","author":"C Platell","year":"2000","unstructured":"Platell C, Kong SE, McCauley R, Hall JC (2000) Branched-chain amino acids. J Gastroenterol Hepatol 15(7):706\u2013717. https:\/\/doi.org\/10.1046\/j.1440-1746.2000.02205.x","journal-title":"J Gastroenterol Hepatol"},{"issue":"12","key":"9725_CR19","doi-asserted-by":"publisher","first-page":"2733","DOI":"10.1002\/ijc.22227","volume":"119","author":"A Ramos-Montoya","year":"2006","unstructured":"Ramos-Montoya A, Lee WN, Bassilian S, Lim S, Trebukhina RV, Kazhyna MV, Ciudad CJ, No\u00e9 V, Centelles JJ, Cascante M (2006) Pentose phosphate cycle oxidative and nonoxidative balance: a new vulnerable target for overcoming drug resistance in cancer. Int J Cancer 119(12):2733\u20132741. https:\/\/doi.org\/10.1002\/ijc.22227","journal-title":"Int J Cancer"},{"issue":"9","key":"9725_CR20","doi-asserted-by":"publisher","first-page":"849","DOI":"10.1056\/NEJMra1703413","volume":"377","author":"M Reck","year":"2017","unstructured":"Reck M, Rabe KF (2017) Precision diagnosis and treatment for advanced non-small-cell lung cancer. N Engl J Med 377(9):849\u2013861. https:\/\/doi.org\/10.1056\/NEJMra1703413","journal-title":"N Engl J Med"},{"issue":"5","key":"9725_CR21","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1007\/s10585-015-9718-1","volume":"32","author":"C Ricciardelli","year":"2015","unstructured":"Ricciardelli C, Lokman NA, Cheruvu S, Tan IA, Ween MP, Pyragius CE, Ruszkiewicz A, Hoffmann P, Oehler MK (2015) Transketolase is upregulated in metastatic peritoneal implants and promotes ovarian cancer cell proliferation. Clin Exp Metas 32(5):441\u2013455. https:\/\/doi.org\/10.1007\/s10585-015-9718-1","journal-title":"Clin Exp Metas"},{"issue":"3","key":"9725_CR22","doi-asserted-by":"publisher","first-page":"977","DOI":"10.1016\/j.bmc.2016.12.010","volume":"25","author":"AV Subba Rao","year":"2017","unstructured":"Subba Rao AV, Swapna K, Shaik SP, Lakshma Nayak V, Srinivasa Reddy T, Sunkari S, Shaik TB, Bagul C, Kamal A (2017) Synthesis and biological evaluation of cis-restricted triazole\/tetrazole mimics of combretastatin-benzothiazole hybrids as tubulin polymerization inhibitors and apoptosis inducers. Bioorg Med Chem 25(3):977\u2013999. https:\/\/doi.org\/10.1016\/j.bmc.2016.12.010","journal-title":"Bioorg Med Chem"},{"issue":"5","key":"9725_CR23","doi-asserted-by":"publisher","first-page":"903","DOI":"10.1016\/j.cmet.2019.08.014","volume":"30","author":"RC Sun","year":"2019","unstructured":"Sun RC, Dukhande VV, Zhou Z, Young L, Emanuelle S, Brainson CF, Gentry MS (2019) Nuclear glycogenolysis modulates histone acetylation in human non-small cell lung cancers. Cell Metab 30(5):903-916.e7. https:\/\/doi.org\/10.1016\/j.cmet.2019.08.014","journal-title":"Cell Metab"},{"issue":"6","key":"9725_CR24","doi-asserted-by":"publisher","first-page":"2206","DOI":"10.1016\/j.bmcl.2007.11.101","volume":"18","author":"AA Thomas","year":"2008","unstructured":"Thomas AA, Le Huerou Y, De Meese J, Gunawardana I, Kaplan T, Romoff TT, Gonzales SS, Condroski K, Boyd SA, Ballard J, Bernat B, DeWolf W, Han M, Lee P, Lemieux C, Pedersen R, Pheneger J, Poch G, Smith D, Sullivan F, Weiler S, Wright SK, Lin J, Brandhuber B, Vigers G (2008) Synthesis, in vitro and in vivo activity of thiamine antagonist transketolase inhibitors. Bioorg Med Chem Lett 18(6):2206\u20132210. https:\/\/doi.org\/10.1016\/j.bmcl.2007.11.101","journal-title":"Bioorg Med Chem Lett"},{"key":"9725_CR25","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1186\/2162-3619-2-18","volume":"2","author":"J Wang","year":"2013","unstructured":"Wang J, Zhang X, Ma D, Lee WP, Xiao J, Zhao Y, Go VL, Wang Q, Yen Y, Recker R, Xiao GG (2013) Inhibition of transketolase by oxythiamine altered dynamics of protein signals in pancreatic cancer cells. Exp Hematol Oncol 2:18. https:\/\/doi.org\/10.1186\/2162-3619-2-18","journal-title":"Exp Hematol Oncol"},{"issue":"5","key":"9725_CR26","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1007\/s10585-010-9331-2","volume":"27","author":"CM Yang","year":"2010","unstructured":"Yang CM, Liu YZ, Liao JW, Hu ML (2010) The in vitro and in vivo anti-metastatic efficacy of oxythiamine and the possible mechanisms of action. Clin Exp Metas 27(5):341\u2013349. https:\/\/doi.org\/10.1007\/s10585-010-9331-2","journal-title":"Clin Exp Metas"},{"issue":"6","key":"9725_CR27","doi-asserted-by":"publisher","first-page":"e2002711","DOI":"10.1371\/journal.pbio.2002711","volume":"15","author":"S Zargarian","year":"2017","unstructured":"Zargarian S, Shlomovitz I, Erlich Z, Hourizadeh A, Ofir-Birin Y, Croker BA, Regev-Rudzki N, Edry-Botzer L, Gerlic M (2017) Phosphatidylserine externalization, \u201cnecroptotic bodies\u201d release, and phagocytosis during necroptosis. PLoS Biol 15(6):e2002711. https:\/\/doi.org\/10.1371\/journal.pbio.2002711","journal-title":"PLoS Biol"},{"issue":"1","key":"9725_CR28","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1186\/2049-3002-1-16","volume":"1","author":"JA Zastre","year":"2013","unstructured":"Zastre JA, Sweet RL, Hanberry BS, Ye S (2013) Linking vitamin B1 with cancer cell metabolism. Cancer Metab 1(1):16. https:\/\/doi.org\/10.1186\/2049-3002-1-16","journal-title":"Cancer Metab"},{"issue":"2","key":"9725_CR29","doi-asserted-by":"publisher","first-page":"980","DOI":"10.1021\/pr9008805","volume":"9","author":"H Zhang","year":"2010","unstructured":"Zhang H, Cao R, Lee WN, Deng C, Zhao Y, Lappe J, Recker R, Yen Y, Wang Q, Tsai MY, Go VL, Xiao GG (2010) Inhibition of protein phosphorylation in MIA pancreatic cancer cells: confluence of metabolic and signaling pathways. J Proteome Res 9(2):980\u2013989. https:\/\/doi.org\/10.1021\/pr9008805","journal-title":"J Proteome Res"},{"issue":"20","key":"9725_CR30","doi-asserted-by":"publisher","first-page":"2962","DOI":"10.1038\/onc.2010.67","volume":"29","author":"F Zhao","year":"2010","unstructured":"Zhao F, Mancuso A, Bui TV, Tong X, Gruber JJ, Swider CR, Sanchez PV, Lum JJ, Sayed N, Melo JV, Perl AE, Carroll M, Tuttle SW, Thompson CB (2010) Imatinib resistance associated with BCR-ABL upregulation is dependent on HIF-1alpha-induced metabolic reprograming. Oncogene 29(20):2962\u20132972. https:\/\/doi.org\/10.1038\/onc.2010.67","journal-title":"Oncogene"}],"container-title":["Cognitive Neurodynamics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11571-021-09725-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11571-021-09725-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11571-021-09725-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,19]],"date-time":"2022-05-19T19:30:19Z","timestamp":1652988619000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11571-021-09725-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,9]]},"references-count":30,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2022,6]]}},"alternative-id":["9725"],"URL":"https:\/\/doi.org\/10.1007\/s11571-021-09725-7","relation":{},"ISSN":["1871-4080","1871-4099"],"issn-type":[{"value":"1871-4080","type":"print"},{"value":"1871-4099","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,9]]},"assertion":[{"value":"12 July 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 September 2021","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 September 2021","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 November 2021","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"No conflict of interest needs to declare.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}