{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T23:01:46Z","timestamp":1792623706389,"version":"4.5.0"},"reference-count":44,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2015,3,19]],"date-time":"2015-03-19T00:00:00Z","timestamp":1426723200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Cancer"],"published-print":{"date-parts":[[2015,12]]},"DOI":"10.1186\/s12943-015-0331-3","type":"journal-article","created":{"date-parts":[[2015,3,18]],"date-time":"2015-03-18T01:33:48Z","timestamp":1426642428000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["Dichloroacetate restores drug sensitivity in paclitaxel-resistant cells by inducing citric acid accumulation"],"prefix":"10.1186","volume":"14","author":[{"given":"Xiang","family":"Zhou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruohua","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenhai","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiajin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoping","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaoli","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianjun","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,3,19]]},"reference":[{"key":"331_CR1","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1126\/science.123.3191.309","volume":"123","author":"O Warburg","year":"1956","unstructured":"Warburg O. On the origin of cancer cells. Science. 1956;123:309\u201314.","journal-title":"Science"},{"key":"331_CR2","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1038\/nrc2981","volume":"11","author":"RA Cairns","year":"2011","unstructured":"Cairns RA, Harris IS, Mak TW. Regulation of cancer cell metabolism. Nat Rev Cancer. 2011;11:85\u201395.","journal-title":"Nat Rev Cancer"},{"key":"331_CR3","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1016\/j.semcdb.2012.02.003","volume":"23","author":"SJ Bensinger","year":"2012","unstructured":"Bensinger SJ, Christofk HR. New aspects of the Warburg effect in cancer cell biology. Semin Cell Dev Biol. 2012;23:352\u201361.","journal-title":"Semin Cell Dev Biol"},{"key":"331_CR4","doi-asserted-by":"publisher","first-page":"1766","DOI":"10.2967\/jnumed.114.145490","volume":"55","author":"X Zhou","year":"2014","unstructured":"Zhou X, Chen R, Xie W, Ni Y, Liu J, Huang G. Relationship between 18\u00a0F-FDG accumulation and lactate dehydrogenase A expression in lung adenocarcinomas, the. J Nucl Med. 2014;55:1766\u201371.","journal-title":"J Nucl Med"},{"key":"331_CR5","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1016\/j.ccr.2006.04.023","volume":"9","author":"VR Fantin","year":"2006","unstructured":"Fantin VR, St-Pierre J, Leder P. Attenuation of LDH-A expression uncovers a link between glycolysis, mitochondrial physiology, and tumor maintenance. Cancer Cell. 2006;9:425\u201334.","journal-title":"Cancer Cell"},{"key":"331_CR6","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1016\/j.bbrc.2003.11.136","volume":"313","author":"XL Zu","year":"2004","unstructured":"Zu XL, Guppy M. Cancer metabolism: facts, fantasy, and fiction. Biochem Biophys Res Commun. 2004;313:459\u201365.","journal-title":"Biochem Biophys Res Commun"},{"key":"331_CR7","doi-asserted-by":"publisher","first-page":"1437","DOI":"10.1038\/sj.leu.2403043","volume":"17","author":"JS Carew","year":"2003","unstructured":"Carew JS, Zhou Y, Albitar M, Carew JD, Keating MJ, Huang P. Mitochondrial DNA mutations in primary leukemia cells after chemotherapy: clinical significance and therapeutic implications. Leukemia. 2003;17:1437\u201347.","journal-title":"Leukemia"},{"key":"331_CR8","doi-asserted-by":"publisher","first-page":"989","DOI":"10.1038\/sj.bjc.6604554","volume":"99","author":"ED Michelakis","year":"2008","unstructured":"Michelakis ED, Webster L, Mackey JR. Dichloroacetate (DCA) as a potential metabolic-targeting therapy for cancer. Brit J Cancer. 2008;99:989\u201394.","journal-title":"Brit J Cancer"},{"key":"331_CR9","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1177\/0091270003254637","volume":"43","author":"PW Stacpoole","year":"2003","unstructured":"Stacpoole PW, Nagaraja NV, Hutson AD. Efficacy of dichloroacetate as a lactate-lowering drug. J Clin Pharmacol. 2003;43:683\u201391.","journal-title":"J Clin Pharmacol"},{"key":"331_CR10","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.ccr.2006.10.020","volume":"11","author":"S Bonnet","year":"2007","unstructured":"Bonnet S, Archer SL, Allalunis-Turner J, Haromy A, Beaulieu C, Thompson R, et al. A mitochondria-K+ channel axis is suppressed in cancer and its normalization promotes apoptosis and inhibits cancer growth. Cancer Cell. 2007;11:37\u201351.","journal-title":"Cancer Cell"},{"key":"331_CR11","doi-asserted-by":"publisher","first-page":"1124","DOI":"10.1016\/0026-0495(89)90051-6","volume":"38","author":"PW Stacpoole","year":"1989","unstructured":"Stacpoole PW. The pharmacology of dichloroacetate. Metabolism. 1989;38:1124\u201344.","journal-title":"Metabolism"},{"key":"331_CR12","doi-asserted-by":"publisher","first-page":"1223","DOI":"10.1002\/pros.20788","volume":"68","author":"WG Cao","year":"2008","unstructured":"Cao WG, Yacoub S, Shiverick KT, Namiki K, Sakai Y, Porvasnik S, et al. Dichloroacetate (DCA) sensitizes both wild-type and over expressing Bcl-2 prostate cancer cells in vitro to radiation. Prostate. 2008;68:1223\u201331.","journal-title":"Prostate"},{"key":"331_CR13","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1186\/1471-2407-11-235","volume":"11","author":"IF Robey","year":"2011","unstructured":"Robey IF, Martin NK. Bicarbonate and dichloroacetate: evaluating pH altering therapies in a mouse model for metastatic breast cancer. BMC Cancer. 2011;11:235.","journal-title":"BMC Cancer"},{"key":"331_CR14","doi-asserted-by":"publisher","first-page":"1746","DOI":"10.1038\/sj.bjc.6605701","volume":"102","author":"BM Madhok","year":"2010","unstructured":"Madhok BM, Yeluri S, Perry SL, Hughes TA, Jayne DG. Dichloroacetate induces apoptosis and cell-cycle arrest in colorectal cancer cells. Brit J Cancer. 2010;102:1746\u201352.","journal-title":"Brit J Cancer"},{"key":"331_CR15","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1016\/j.ygyno.2008.01.038","volume":"109","author":"JY Wong","year":"2008","unstructured":"Wong JY, Huggins GS, Debidda M, Munshi NC, De Vivo I. Dichloroacetate induces apoptosis in endometrial cancer cells. Gynecol Oncol. 2008;109:394\u2013402.","journal-title":"Gynecol Oncol"},{"key":"331_CR16","doi-asserted-by":"publisher","first-page":"7170","DOI":"10.1158\/1078-0432.CCR-09-1676","volume":"15","author":"RA Cairns","year":"2009","unstructured":"Cairns RA, Bennewith KL, Graves EE, Giaccia AJ, Chang DT, Denko NC. Pharmacologically increased tumor hypoxia Can Be measured by F-18-fluoroazomycin arabinoside positron emission tomography and enhances tumor response to hypoxic cytotoxin PR-104. Clin Cancer Res. 2009;15:7170\u20134.","journal-title":"Clin Cancer Res"},{"key":"331_CR17","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1007\/s00280-010-1361-6","volume":"67","author":"D Heshe","year":"2011","unstructured":"Heshe D, Hoogestraat S, Brauckmann C, Karst U, Boos J, Lanvers-Kaminsky C. Dichloroacetate metabolically targeted therapy defeats cytotoxicity of standard anticancer drugs. Cancer Chemother Pharmacol. 2011;67:647\u201355.","journal-title":"Cancer Chemother Pharmacol"},{"key":"331_CR18","doi-asserted-by":"publisher","first-page":"2510","DOI":"10.1002\/ijc.25499","volume":"127","author":"LH Stockwin","year":"2010","unstructured":"Stockwin LH, Yu SX, Borgel S, Hancock C, Wolfe TL, Phillips LR, et al. Sodium dichloroacetate selectively targets cells with defects in the mitochondrial ETC. Int J Cancer. 2010;127:2510\u20139.","journal-title":"Int J Cancer"},{"key":"331_CR19","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1007\/978-0-387-74039-3_9","volume":"608","author":"M Tan","year":"2007","unstructured":"Tan M, Yu D. Molecular mechanisms of ErbB2-Mediated breast cancer chemoresistance. Breast Cancer Chemosensitivity. 2007;608:119\u201329.","journal-title":"Breast Cancer Chemosensitivity"},{"key":"331_CR20","doi-asserted-by":"publisher","first-page":"872","DOI":"10.1177\/0091270005276905","volume":"45","author":"VS Donnenberg","year":"2005","unstructured":"Donnenberg VS, Donnenberg AD. Multiple drug resistance in cancer revisited: the cancer stem cell hypothesis. J Clin Pharmacol. 2005;45:872\u20137.","journal-title":"J Clin Pharmacol"},{"key":"331_CR21","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1016\/j.critrevonc.2009.11.006","volume":"75","author":"DJ Stewart","year":"2010","unstructured":"Stewart DJ. Tumor and host factors that may limit efficacy of chemotherapy in non-small cell and small cell lung cancer. Crit Rev Oncol Hemat. 2010;75:173\u2013234.","journal-title":"Crit Rev Oncol Hemat"},{"key":"331_CR22","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1007\/s00432-010-0913-9","volume":"137","author":"QL Sun","year":"2011","unstructured":"Sun QL, Sha HF, Yang XH, Bao GL, Lu J, Xie YY. Comparative proteomic analysis of paclitaxel sensitive A549 lung adenocarcinoma cell line and its resistant counterpart A549-Taxol. J Cancer Res Clin. 2011;137:521\u201332.","journal-title":"J Cancer Res Clin"},{"key":"331_CR23","doi-asserted-by":"publisher","first-page":"814","DOI":"10.1038\/sj.bjc.6690769","volume":"81","author":"J Tian","year":"1999","unstructured":"Tian J, Tang ZY, Ye SL, Liu YK, Lin ZY, Chen J, et al. New human hepatocellular carcinoma (HCC) cell line with highly metastatic potential (MHCC97) and its expressions of the factors associated with metastasis. Brit J Cancer. 1999;81:814\u201321.","journal-title":"Brit J Cancer"},{"key":"331_CR24","doi-asserted-by":"publisher","first-page":"e74623","DOI":"10.1371\/journal.pone.0074623","volume":"8","author":"J Li","year":"2013","unstructured":"Li J, Zhao S, Zhou X, Zhang T, Zhao L, Miao P, et al. Inhibition of lipolysis by mercaptoacetate and etomoxir specifically sensitize drug-resistant lung adenocarcinoma cell to paclitaxel. PLoS One. 2013;8:e74623.","journal-title":"PLoS One"},{"key":"331_CR25","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1158\/0008-5472.CAN-04-4313","volume":"65","author":"RH Xu","year":"2005","unstructured":"Xu RH, Pelicano H, Zhou Y, Carew JS, Feng L, Bhalla KN, et al. Inhibition of glycolysis in cancer cells: a novel strategy to overcome drug resistance associated with mitochondrial respiratory defect and hypoxia. Cancer Res. 2005;65:613\u201321.","journal-title":"Cancer Res"},{"key":"331_CR26","doi-asserted-by":"publisher","first-page":"1132","DOI":"10.1016\/j.febslet.2009.02.043","volume":"583","author":"QQ Zhou","year":"2009","unstructured":"Zhou QQ, Lam PY, Han D, Cadenas E. Activation of c-Jun-N-terminal kinase and decline of mitochondrial pyruvate dehydrogenase activity during brain aging. FEBS Lett. 2009;583:1132\u201340.","journal-title":"FEBS Lett"},{"key":"331_CR27","doi-asserted-by":"publisher","first-page":"35406","DOI":"10.1074\/jbc.M113.508226","volume":"288","author":"ZH Yu","year":"2013","unstructured":"Yu ZH, Zhao XP, Huang LQ, Zhang T, Yang FJ, Xie L, et al. Proviral Insertion in Murine Lymphomas 2 (PIM2) Oncogene Phosphorylates Pyruvate Kinase M2 (PKM2) and promotes glycolysis in cancer cells. J Biol Chem. 2013;288:35406\u201316.","journal-title":"J Biol Chem"},{"key":"331_CR28","doi-asserted-by":"publisher","first-page":"e92949","DOI":"10.1371\/journal.pone.0092949","volume":"9","author":"L Huang","year":"2014","unstructured":"Huang L, Yu Z, Zhang T, Zhao X, Huang G. HSP40 interacts with pyruvate kinase M2 and regulates glycolysis and cell proliferation in tumor cells. PLoS One. 2014;9:e92949.","journal-title":"PLoS One"},{"key":"331_CR29","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1038\/nature10602","volume":"481","author":"CM Metallo","year":"2012","unstructured":"Metallo CM, Gameiro PA, Bell EL, Mattaini KR, Yang JJ, Hiller K, et al. Reductive glutamine metabolism by IDH1 mediates lipogenesis under hypoxia. Nature. 2012;481:380\u2013U166.","journal-title":"Nature"},{"key":"331_CR30","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/S0006-8993(01)01983-7","volume":"894","author":"A Waki","year":"2001","unstructured":"Waki A, Yano R, Yoshimoto M, Sadato N, Yonekura Y, Fujibayashi Y. Dynamic changes in glucose metabolism accompanying the expression of the neural phenotype after differentiation in PC12 cells. Brain Res. 2001;894:88\u201394.","journal-title":"Brain Res"},{"key":"331_CR31","first-page":"646","volume":"42","author":"DE Lorke","year":"2001","unstructured":"Lorke DE, Kruger M, Buchert R, Bohuslavizki KH, Clausen M, Schumacher U. In vitro and in vivo tracer characteristics of an established multidrug-resistant human colon cancer cell line. J Nucl Med. 2001;42:646\u201354.","journal-title":"J Nucl Med"},{"key":"331_CR32","first-page":"4595","volume":"53","author":"F Hyafil","year":"1993","unstructured":"Hyafil F, Vergely C, Du Vignaud P, Grand-Perret T. In vitro and in vivo reversal of multidrug resistance by GF120918, an acridonecarboxamide derivative. Cancer Res. 1993;53:4595\u2013602.","journal-title":"Cancer Res"},{"key":"331_CR33","doi-asserted-by":"publisher","first-page":"10387","DOI":"10.1158\/0008-5472.CAN-68-24-COR","volume":"68","author":"C Dai","year":"2008","unstructured":"Dai C, Tiwari AK, Wu CP, Su X, Wang SR, Liu D, et al. Lapatinib (Tykerb, GW572016) reverses multidrug resistance in cancer cells by inhibiting the activity of ATP-binding cassette subfamily B member 1 and G member 2 (vol 68, pg 7905, 2008). Cancer Res. 2008;68:10387.","journal-title":"Cancer Res"},{"key":"331_CR34","doi-asserted-by":"publisher","first-page":"1560","DOI":"10.1016\/j.cellsig.2014.03.016","volume":"26","author":"Z Yu","year":"2014","unstructured":"Yu Z, Ge Y, Xie L, Zhang T, Huang L, Zhao X, et al. Using a yeast two-hybrid system to identify FTCD as a new regulator for HIF-1alpha in HepG2 cells. Cell Signal. 2014;26:1560\u20136.","journal-title":"Cell Signal"},{"key":"331_CR35","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1159\/000119756","volume":"81","author":"HS Kim","year":"2008","unstructured":"Kim HS, Oh JM, Jin DH, Yang KH, Moon EY. Paclitaxel induces vascular endothelial growth factor expression through reactive oxygen species production. Pharmacology. 2008;81:317\u201324.","journal-title":"Pharmacology"},{"key":"331_CR36","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1016\/j.semcancer.2008.11.008","volume":"19","author":"C Frezza","year":"2009","unstructured":"Frezza C, Gottlieb E. Mitochondria in cancer: not just innocent bystanders. Semin Cancer Biol. 2009;19:4\u201311.","journal-title":"Semin Cancer Biol"},{"key":"331_CR37","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1038\/nrd3137","volume":"9","author":"S Fulda","year":"2010","unstructured":"Fulda S, Galluzzi L, Kroemer G. Targeting mitochondria for cancer therapy. Nat Rev Drug Discov. 2010;9:447\u201364.","journal-title":"Nat Rev Drug Discov"},{"key":"331_CR38","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1038\/nrc2789","volume":"10","author":"JI Fletcher","year":"2010","unstructured":"Fletcher JI, Haber M, Henderson MJ, Norris MD. ABC transporters in cancer: more than just drug efflux pumps. Nat Rev Cancer. 2010;10:147\u201356.","journal-title":"Nat Rev Cancer"},{"key":"331_CR39","first-page":"111","volume":"1825","author":"P Icard","year":"2012","unstructured":"Icard P, Poulain L, Lincet H. Understanding the central role of citrate in the metabolism of cancer cells. Bba-Rev Cancer. 2012;1825:111\u20136.","journal-title":"Bba-Rev Cancer"},{"key":"331_CR40","first-page":"797","volume":"31","author":"Y Lu","year":"2011","unstructured":"Lu Y, Zhang X, Zhang H, Lan J, Huang G, Varin E, et al. Citrate induces apoptotic cell death: a promising way to treat gastric carcinoma? Anticancer Res. 2011;31:797\u2013805.","journal-title":"Anticancer Res"},{"key":"331_CR41","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1042\/bj3290191","volume":"329","author":"MM Bowker-Kinley","year":"1998","unstructured":"Bowker-Kinley MM, Davis WI, Wu PF, Harris RA, Popov KM. Evidence for existence of tissue-specific regulation of the mammalian pyruvate dehydrogenase complex. Biochem J. 1998;329:191\u20136.","journal-title":"Biochem J"},{"key":"331_CR42","doi-asserted-by":"publisher","first-page":"3985","DOI":"10.1038\/onc.2011.167","volume":"30","author":"A Lemarie","year":"2011","unstructured":"Lemarie A, Grimm S. Mitochondrial respiratory chain complexes: apoptosis sensors mutated in cancer. Oncogene. 2011;30:3985\u20134003.","journal-title":"Oncogene"},{"key":"331_CR43","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1158\/0008-5472.CAN-11-1674","volume":"72","author":"Y Zhou","year":"2012","unstructured":"Zhou Y, Tozzi F, Chen J, Fan F, Xia L, Wang J, et al. Intracellular ATP levels are a pivotal determinant of chemoresistance in colon cancer cells. Cancer Res. 2012;72:304\u201314.","journal-title":"Cancer Res"},{"key":"331_CR44","doi-asserted-by":"publisher","first-page":"e27222","DOI":"10.1371\/journal.pone.0027222","volume":"6","author":"A Nakano","year":"2011","unstructured":"Nakano A, Tsuji D, Miki H, Cui Q, El Sayed SM, Ikegame A, et al. Glycolysis inhibition inactivates ABC transporters to restore drug sensitivity in malignant cells. PLoS ONE. 2011;6:e27222.","journal-title":"PLoS ONE"}],"container-title":["Molecular Cancer"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12943-015-0331-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s12943-015-0331-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12943-015-0331-3","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12943-015-0331-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,2]],"date-time":"2021-09-02T09:35:14Z","timestamp":1630575314000},"score":1,"resource":{"primary":{"URL":"https:\/\/molecular-cancer.biomedcentral.com\/articles\/10.1186\/s12943-015-0331-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,3,19]]},"references-count":44,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2015,12]]}},"alternative-id":["331"],"URL":"https:\/\/doi.org\/10.1186\/s12943-015-0331-3","relation":{},"ISSN":["1476-4598"],"issn-type":[{"value":"1476-4598","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,3,19]]},"assertion":[{"value":"17 July 2014","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 March 2015","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 March 2015","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"63"}}