{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T15:14:50Z","timestamp":1789658090973,"version":"4.0.1"},"reference-count":45,"publisher":"Japanese Pharmacological Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Pharmacol Sci"],"published-print":{"date-parts":[[2013]]},"DOI":"10.1254\/jphs.12149fp","type":"journal-article","created":{"date-parts":[[2013,4,18]],"date-time":"2013-04-18T23:04:52Z","timestamp":1366326292000},"page":"247-256","source":"Crossref","is-referenced-by-count":87,"title":["Inhibition of the PI3K\/AKT-NF-\u03baB Pathway With Curcumin Enhanced Radiation-Induced Apoptosis in Human Burkitt\u2019s Lymphoma"],"prefix":"10.1254","volume":"121","author":[{"given":"Qiao","family":"Qiao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanjun","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"332","reference":[{"key":"1","doi-asserted-by":"crossref","unstructured":"1 Cerny T, Gillessen S. Advances in the treatment of non-Hodgkin\u2019s lymphoma. Ann Oncol. 2002;13 Suppl 4:211\u2013216.","DOI":"10.1093\/annonc\/mdf662"},{"key":"2","doi-asserted-by":"crossref","unstructured":"2 Hainsworth JD. Monoclonal antibody therapy in lymphoid malignancies. Oncologist. 2000;5:376\u2013384.","DOI":"10.1634\/theoncologist.5-5-376"},{"key":"3","doi-asserted-by":"crossref","unstructured":"3 Lowry L, Smith P, Qian W, Falk S, Benstead K, Illidge T, et al. Reduced dose radiotherapy for local control in non-Hodgkin lymphoma: a randomised phase III trial. Radiother Oncol. 2011;100:86\u201392.","DOI":"10.1016\/j.radonc.2011.05.013"},{"key":"4","doi-asserted-by":"crossref","unstructured":"4 Li HF, Kim JS, Waldman T. Radiation-induced Akt activation modulates radioresistance in human glioblastoma cells. Radiat Oncol. 2009;4:43.","DOI":"10.1186\/1748-717X-4-43"},{"key":"5","doi-asserted-by":"crossref","unstructured":"5 Cantley LC. The phosphoinositide 3-kinase pathway. Science. 2002;296:1655\u20131657.","DOI":"10.1126\/science.296.5573.1655"},{"key":"6","doi-asserted-by":"crossref","unstructured":"6 Schatz JH. Targeting the PI3K\/AKT\/mTOR pathway in non-Hodgkin\u2019s lymphoma: results, biology, and development strategies. Curr Oncol Rep. 2011;13:398\u2013406.","DOI":"10.1007\/s11912-011-0187-7"},{"key":"7","doi-asserted-by":"crossref","unstructured":"7 Drakos E, Rassidakis GZ, Medeiros LJ. Mammalian target of rapamycin (mTOR) pathway signalling in lymphomas. Expert Rev Mol Med. 2008;10:e4.","DOI":"10.1017\/S1462399408000586"},{"key":"8","doi-asserted-by":"crossref","unstructured":"8 Suzuki E, Umezawa K, Bonavida B. Rituximab inhibits the constitutively activated PI3K-Akt pathway in B-NHL cell lines: involvement in chemosensitization to drug-induced apoptosis. Oncogene. 2007;26:6184\u20136193.","DOI":"10.1038\/sj.onc.1210448"},{"key":"9","doi-asserted-by":"crossref","unstructured":"9 Kang HW, Kim JM, Cha MY, Jung HC, Song IS, Kim JS. Deguelin, an Akt inhibitor, down-regulates NF-kappaB signaling and induces apoptosis in colon cancer cells and inhibits tumor growth in mice. Dig Dis Sci. 2012;57:2873\u20132882.","DOI":"10.1007\/s10620-012-2237-x"},{"key":"10","doi-asserted-by":"crossref","unstructured":"10 Liu CJ, Lo JF, Kuo CH, Chu CH, Chen LM, Tsai FJ, et al. Akt mediates 17beta-estradiol and\/or estrogen receptor-alpha inhibition of LPS-induced tumor necresis factor-alpha expression and myocardial cell apoptosis by suppressing the JNK1\/2-NFkappaB pathway. J Cell Mol Med. 2009;13:3655\u20133667.","DOI":"10.1111\/j.1582-4934.2009.00669.x"},{"key":"11","doi-asserted-by":"crossref","unstructured":"11 Uddin S, Hussain AR, Siraj AK, Manogaran PS, Al-Jomah NA, Moorji A, et al. Role of phosphatidylinositol 3\u2032-kinase\/AKT pathway in diffuse large B-cell lymphoma survival. Blood. 2006;108:4178\u20134186.","DOI":"10.1182\/blood-2006-04-016907"},{"key":"12","doi-asserted-by":"crossref","unstructured":"12 Engelman JA. Targeting PI3K signalling in cancer: opportunities, challenges and limitations. Nat Rev Cancer. 2009;9:550\u2013562.","DOI":"10.1038\/nrc2664"},{"key":"13","doi-asserted-by":"crossref","unstructured":"13 Qiao Q, Jiang Y, Li G. Curcumin improves the antitumor effect of X-ray irradiation by blocking the NF-kappaB pathway: an in-vitro study of lymphoma. Anticancer Drugs. 2012;23:597\u2013605.","DOI":"10.1097\/CAD.0b013e3283503fbc"},{"key":"14","doi-asserted-by":"crossref","unstructured":"14 Kane LP, Shapiro VS, Stokoe D, Weiss A. Induction of NF-kappaB by the Akt\/PKB kinase. Curr Biol. 1999;9:601\u2013604.","DOI":"10.1016\/S0960-9822(99)80265-6"},{"key":"15","doi-asserted-by":"crossref","unstructured":"15 Qiao Q, Nozaki Y, Sakoe K, Komatsu N, Kirito K. NF-kappaB mediates aberrant activation of HIF-1 in malignant lymphoma. Exp Hematol. 2010;38:1199\u20131208.","DOI":"10.1016\/j.exphem.2010.08.007"},{"key":"16","doi-asserted-by":"crossref","unstructured":"16 Liu X, Shi Y, Birnbaum MJ, Ye K, De Jong R, Oltersdorf T, et al. Quantitative analysis of anti-apoptotic function of Akt in Akt1 and Akt2 double knock-out mouse embryonic fibroblast cells under normal and stressed conditions. J Biol Chem. 2006;281:31380\u201331388.","DOI":"10.1074\/jbc.M606603200"},{"key":"17","doi-asserted-by":"crossref","unstructured":"17 Sadidi M, Lentz SI, Feldman EL. Hydrogen peroxide-induced Akt phosphorylation regulates Bax activation. Biochimie. 2009;91:577\u2013585.","DOI":"10.1016\/j.biochi.2009.01.010"},{"key":"18","doi-asserted-by":"crossref","unstructured":"18 Chin AC, Flynn AN, Fedwick JP, Buret AG. The role of caspase-3 in lipopolysaccharide-mediated disruption of intestinal epithelial tight junctions. Can J Physiol Pharmacol. 2006;84:1043\u20131050.","DOI":"10.1139\/y06-056"},{"key":"19","doi-asserted-by":"crossref","unstructured":"19 Bavi P, Uddin S, Bu R, Ahmed M, Abubaker J, Balde V, et al. The biological and clinical impact of inhibition of NF-kappaB-initiated apoptosis in diffuse large B cell lymphoma (DLBCL). J Pathol. 2011;224:355\u2013366.","DOI":"10.1002\/path.2864"},{"key":"20","doi-asserted-by":"crossref","unstructured":"20 Yu S, Shen G, Khor TO, Kim JH, Kong AN. Curcumin inhibits Akt\/mTOR signaling through protein phosphatase-dependent mechanism. Mol Cancer Ther. 2008;7:2609\u20132620.","DOI":"10.1158\/1535-7163.MCT-07-2400"},{"key":"21","doi-asserted-by":"crossref","unstructured":"21 Wong TF, Takeda T, Li B, Tsuiji K, Kitamura M, Kondo A, et al. Curcumin disrupts uterine leiomyosarcoma cells through AKT-mTOR pathway inhibition. Gynecol Oncol. 2001;122:141\u2013148.","DOI":"10.1016\/j.ygyno.2011.03.001"},{"key":"22","doi-asserted-by":"crossref","unstructured":"22 Prakobwong S, Gupta SC, Kim JH, Sung B, Pinlaor P, Hiraku Y, et al. Curcumin suppresses proliferation and induces apoptosis in human biliary cancer cells through modulation of multiple cell signaling pathways. Carcinogenesis. 2011;32:1372\u20131380.","DOI":"10.1093\/carcin\/bgr032"},{"key":"23","doi-asserted-by":"crossref","unstructured":"23 Mimeault M, Batra SK. Potential applications of curcumin and its novel synthetic analogs and nanotechnology-based formulations in cancer prevention and therapy. Chin Med. 2011;6:31.","DOI":"10.1186\/1749-8546-6-31"},{"key":"24","doi-asserted-by":"crossref","unstructured":"24 Goel A, Aggarwal BB. Curcumin, the golden spice from Indian saffron, is a chemosensitizer and radiosensitizer for tumors and chemoprotector and radioprotector for normal organs. Nutr Cancer. 2010;62:919\u2013930.","DOI":"10.1080\/01635581.2010.509835"},{"key":"25","doi-asserted-by":"crossref","unstructured":"25 Nautiyal J, Banerjee S, Kanwar SS, Yu Y, Patel BB, Sarkar FH, et al. Curcumin enhances dasatinib-induced inhibition of growth and transformation of colon cancer cells. Int J Cancer. 2011;128:951\u2013961.","DOI":"10.1002\/ijc.25410"},{"key":"26","doi-asserted-by":"crossref","unstructured":"26 Se HM, Hyuk SK, Jie WK, Na YK, Do KK, Beob YL, et al. Oral administration of curcumin suppresses production of matrix metalloproteinase (MMP)-1 and MMP-3 to ameliorate collagen-induced arthritis: inhibition of the PKC<i>\u03b4<\/i>\/JNK\/c-Jun pathway. J Pharmacol Sci. 2009;111:13\u201321.","DOI":"10.1254\/jphs.09134FP"},{"key":"27","doi-asserted-by":"crossref","unstructured":"27 Rafiee P, Binion DG, Wellner M, Behmaram B, Floer M, Mitton E, et al. Modulatory effect of curcumin on survival of irradiated human intestinal microvascular endothelial cells: role of Akt\/mTOR and NF-kappaB. Am J Physiol Gastrointest Liver Physiol. 2010;298:G865\u2013G877.","DOI":"10.1152\/ajpgi.00339.2009"},{"key":"28","doi-asserted-by":"crossref","unstructured":"28 Plastaras JP, Dorsey JF, Carroll K, Kim SH, Birnbaum MJ, El-Deiry WS. Role of PI3K\/Akt signaling in TRAIL- and radiation-induced gastrointestinal apoptosis. Cancer Biol Ther. 2008;7:2047\u20132053.","DOI":"10.4161\/cbt.7.12.7570"},{"key":"29","doi-asserted-by":"crossref","unstructured":"29 Fernandez LA, Squatrito M, Northcott P, Awan A, Holland EC, Taylor MD, et al. Oncogenic YAP promotes radioresistance and genomic instability in medulloblastoma through IGF2-mediated Akt activation. Oncogene. 2012;31:1923\u20131937.","DOI":"10.1038\/onc.2011.379"},{"key":"30","doi-asserted-by":"crossref","unstructured":"30 Shimura T, Kakuda S, Ochiai Y, Kuwahara Y, Takai Y, Fukumoto M. Targeting the AKT\/GSK3beta\/cyclin D1\/Cdk4 survival signaling pathway for eradication of tumor radioresistance acquired by fractionated radiotherapy. Int J Radiat Oncol Biol Phys. 2011;80:540\u2013548.","DOI":"10.1016\/j.ijrobp.2010.12.065"},{"key":"31","doi-asserted-by":"crossref","unstructured":"31 Zhan JF, Wu LP, Chen LH, Yuan YW, Xie GZ, Sun AM, et al. Pharmacological inhibition of AKT sensitizes MCF-7 human breast cancer-initiating cells to radiation. Cell Oncol (Dordr). 2011;34:451\u2013456.","DOI":"10.1007\/s13402-011-0020-1"},{"key":"32","doi-asserted-by":"crossref","unstructured":"32 Rudner J, Ruiner CE, Handrick R, Eibl HJ, Belka C, Jendrossek V. The Akt-inhibitor Erufosine induces apoptotic cell death in prostate cancer cells and increases the short term effects of ionizing radiation. Radiat Oncol. 2010;5:108.","DOI":"10.1186\/1748-717X-5-108"},{"key":"33","unstructured":"33 Rashid A, Liu C, Sanli T, Tsiani E, Singh G, Bristow RG, et al. Resveratrol enhances prostate cancer cell response to ionizing radiation. Modulation of the AMPK, Akt and mTOR pathways. Radiat Oncol. 2011;6:144."},{"key":"34","doi-asserted-by":"crossref","unstructured":"34 Nagata Y, Takahashi A, Ohnishi K, Ota I, Ohnishi T, Tojo T, et al. Effect of rapamycin, an mTOR inhibitor, on radiation sensitivity of lung cancer cells having different p53 gene status. Int J Oncol. 2010;37:1001\u20131010.","DOI":"10.3892\/ijo_00000751"},{"key":"35","doi-asserted-by":"crossref","unstructured":"35 Gupta AK, Cerniglia GJ, Mick R, Ahmed MS, Bakanauskas VJ, Muschel RJ, et al. Radiation sensitization of human cancer cells in vivo by inhibiting the activity of PI3K using LY294002. Int J Radiat Oncol Biol Phys. 2003;56:846\u2013853.","DOI":"10.1016\/S0360-3016(03)00214-1"},{"key":"36","doi-asserted-by":"crossref","unstructured":"36 Yin D, Woodruff M, Zhang Y, Whaley S, Miao J, Ferslew K, et al. Morphine promotes Jurkat cell apoptosis through pro-apoptotic FADD\/P53 and anti-apoptotic PI3K\/Akt\/NF-kappaB pathways. J Neuroimmunol. 2006;174:101\u2013107.","DOI":"10.1016\/j.jneuroim.2006.02.001"},{"key":"37","doi-asserted-by":"crossref","unstructured":"37 Kloo B, Nagel D, Pfeifer M, Grau M, Duwel M, Vincendeau M, et al. Critical role of PI3K signaling for NF-kappaB-dependent survival in a subset of activated B-cell-like diffuse large B-cell lymphoma cells. Proc Natl Acad Sci U S A. 2011;108:272\u2013277.","DOI":"10.1073\/pnas.1008969108"},{"key":"38","doi-asserted-by":"crossref","unstructured":"38 Garcia MG, Alaniz LD, Cordo Russo RI, Alvarez E, Hajos SE. PI3K\/Akt inhibition modulates multidrug resistance and activates NF-kappaB in murine lymphoma cell lines. Leuk Res. 2009;33:288\u2013296.","DOI":"10.1016\/j.leukres.2008.06.010"},{"key":"39","doi-asserted-by":"crossref","unstructured":"39 Tadashi Y. Hyaluronan inhibits Akt, leading to nuclear factor-<i>\u03ba<\/i>B down-regulation in lipopolysaccharide-stimulated U937 macrophages. J Pharmacol Sci. 2011;115:509\u2013515.","DOI":"10.1254\/jphs.10244FP"},{"key":"40","doi-asserted-by":"crossref","unstructured":"40 Chao X, Zao J, Xiao-Yi G, Li-Jun M, Tao S. Blocking of PI3K\/AKT induces apoptosis by its effect on NF-kappaB activity in gastric carcinoma cell line SGC7901. Biomed Pharmacother. 2010;64:600\u2013604.","DOI":"10.1016\/j.biopha.2010.08.008"},{"key":"41","doi-asserted-by":"crossref","unstructured":"41 Kazumi M, Fumiko S, Kaori M, Hiroyuki N, Atsufumi K. Curcumin inhibits the proteinase-activated receptor-2\u2013triggered prostaglandin E2 production by suppressing cyclooxygenase-2 upregulation and Akt-dependent activation of nuclear factor-<i>\u03ba<\/i>B in human lung epithelial cells. J Pharmacol Sci. 2010;114:225\u2013229.","DOI":"10.1254\/jphs.10126SC"},{"key":"42","doi-asserted-by":"crossref","unstructured":"42 Weir NM, Selvendiran K, Kutala VK, Tong L, Vishwanath S, Rajaram M, et al. Curcumin induces G2\/M arrest and apoptosis in cisplatin-resistant human ovarian cancer cells by modulating Akt and p38 MAPK. Cancer Biol Ther. 2007;6:178\u2013184.","DOI":"10.4161\/cbt.6.2.3577"},{"key":"43","unstructured":"43 Giri B, Gomes A, Sengupta R, Banerjee S, Nautiyal J, Sarkar FH, et al. Curcumin synergizes the growth inhibitory properties of Indian toad (Bufo melanostictus Schneider) skin-derived factor (BM-ANF1) in HCT-116 colon cancer cells. Anticancer Res. 2009;29:395\u2013401."},{"key":"44","doi-asserted-by":"crossref","unstructured":"44 Zanotto-Filho A, Braganhol E, Edelweiss MI, Behr GA, Zanin R, Schroder R, et al. The curry spice curcumin selectively inhibits cancer cells growth in vitro and in preclinical model of glioblastoma. J Nutr Biochem. 2012;23:591\u2013601.","DOI":"10.1016\/j.jnutbio.2011.02.015"},{"key":"45","unstructured":"45 Lai HW, Chien SY, Kuo SJ, Tseng LM, Lin HY, Chi CW, et al. The potential utility of curcumin in the treatment of HER-2-overexpressed breast cancer: an in vitro and in vivo comparison study with herceptin. Evid Based Complement Alternat Med. 2012;2012:486568."}],"container-title":["Journal of Pharmacological Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/jphs\/121\/4\/121_12149FP\/_pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,5,19]],"date-time":"2021-05-19T15:09:48Z","timestamp":1621436988000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/jphs\/121\/4\/121_12149FP\/_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013]]},"references-count":45,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2013]]}},"URL":"https:\/\/doi.org\/10.1254\/jphs.12149fp","relation":{},"ISSN":["1347-8613","1347-8648"],"issn-type":[{"value":"1347-8613","type":"print"},{"value":"1347-8648","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013]]}}}