{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T03:44:57Z","timestamp":1777434297169,"version":"3.51.4"},"reference-count":70,"publisher":"SAGE Publications","issue":"8","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antioxidants &amp; Redox Signaling"],"published-print":{"date-parts":[[2015,9]]},"abstract":"<jats:p>\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Aims:<\/jats:italic>\n                    <\/jats:bold>\n                    2-Deoxy-\n                    <jats:sc>d<\/jats:sc>\n                    -glucose (2-DG), a synthetic glycolytic inhibitor, is currently under clinical evaluation as a promising anticancer agent. However, 2-DG treatment in cancer cells activates prosurvival Akt signaling that might limit its clinical efficacy. The NADPH oxidase 4 (Nox-4)\/reactive oxygen species\/Akt signaling is known to regulate survival, proliferation, infiltration, and invasion in glioblastomas (GBMs). The enhanced motility, invasiveness, and therapy resistance in GBMs are attributed to metabolic adaptation through increased aerobic glycolysis. Therefore, we hypothesized that inhibition of the Nox-4 might enhance 2-DG-induced suppression of glycolysis, migration, and invasion in GBM cells.\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Results:<\/jats:italic>\n                    <\/jats:bold>\n                    We identified the natural naphthoquinone compound shikonin as a potent inhibitor of the Nox-4\/Akt signaling pathway. The combined treatment of shikonin+2-DG suppressed the glycolytic phenotype, migration, and invasion through modulation of the Akt\/HIF1\u03b1\/hexokinase-2 signaling axis in GBM cells. The combination also exhibited enhanced antiproliferative and antiangiogenic effects\n                    <jats:italic toggle=\"yes\">in vivo.<\/jats:italic>\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Innovation:<\/jats:italic>\n                    <\/jats:bold>\n                    Our data for the first time demonstrate that inhibition of the Nox-4-associated prosurvival signaling pathway by shikonin enhances the antiproliferative and antiangiogenic potential of 2-DG in GBM cells.\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic>\n                    <\/jats:bold>\n                    In summary, the combined inhibition of Nox-4 and glycolysis may have therapeutic implications for the management of GBMs.\n                    <jats:italic toggle=\"yes\">Antioxid. Redox Signal.<\/jats:italic>\n                    23, 665\u2013681.\n                  <\/jats:p>","DOI":"10.1089\/ars.2014.5973","type":"journal-article","created":{"date-parts":[[2015,4,19]],"date-time":"2015-04-19T09:04:54Z","timestamp":1429434294000},"page":"665-681","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":34,"title":["Inhibition of NADPH Oxidase-4 Potentiates 2-Deoxy-\n                    <scp>d<\/scp>\n                    -Glucose-Induced Suppression of Glycolysis, Migration, and Invasion in Glioblastoma Cells: Role of the Akt\/HIF1\u03b1\/HK-2 Signaling Axis"],"prefix":"10.1177","volume":"23","author":[{"given":"Priyanka","family":"Gupta","sequence":"first","affiliation":[{"name":"CSIR-Central Drug Research Institute","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kumaravelu","family":"Jagavelu","sequence":"additional","affiliation":[{"name":"CSIR-Central Drug Research Institute","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Durga Prasad","family":"Mishra","sequence":"additional","affiliation":[{"name":"CSIR-Central Drug Research Institute","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2015,9,10]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6600547"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10495-013-0835-5"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M406486200"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jocn.2012.07.002"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2184.2008.00563.x"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1215\/15228517-2008-106"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.3700355"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2012.157"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-04-0682"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-012-2324-4"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2011.137"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgs274"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.10.5720"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1593\/neo.11134"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-12-0125"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1211\/0022357055119"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.4103\/0973-1482.55136"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-07-4182"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/cgt.2011.59"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-03-2904"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2012.09.022"},{"key":"e_1_3_3_23_2","first-page":"3847","article-title":"The glycolytic phenotype in carcinogenesis and tumor invasion: insights through mathematical models","volume":"63","author":"Gatenby RA","year":"2003","unstructured":"Gatenby RA, and Gawlinski ET. 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