{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T11:10:01Z","timestamp":1751281801990,"version":"3.41.0"},"reference-count":41,"publisher":"Pharmaceutical Society of Japan","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biological & Pharmaceutical Bulletin","Biol. Pharm. Bull."],"published-print":{"date-parts":[[2018]]},"DOI":"10.1248\/bpb.b17-00746","type":"journal-article","created":{"date-parts":[[2018,1,31]],"date-time":"2018-01-31T22:25:50Z","timestamp":1517437550000},"page":"220-228","source":"Crossref","is-referenced-by-count":4,"title":["Assessment of Anticancer Drug Effects on Pancreatic Cancer Cells under Glucose-Depleted Conditions Using Intracellular and Extracellular Amino Acid Metabolomics"],"prefix":"10.1248","volume":"41","author":[{"given":"Ryoko","family":"Tomita","sequence":"first","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, Fukuoka University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenichiro","family":"Todoroki","sequence":"additional","affiliation":[{"name":"Laboratory of Analytical and Bio-Analytical Chemistry, School of Pharmaceutical Sciences, University of Shizuoka"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tadashi","family":"Hayama","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, Fukuoka University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hideyuki","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, Fukuoka University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshihiro","family":"Fujioka","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, Fukuoka University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manabu","family":"Nakashima","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, Fukuoka University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masatoshi","family":"Yamaguchi","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, Fukuoka University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hitoshi","family":"Nohta","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, Fukuoka University"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"163","reference":[{"key":"1","doi-asserted-by":"crossref","unstructured":"1) Vinayavekhin N, Homan EA, Saghatelian A. Exploring disease through metabolomics. ACS Chem. Biol.<\/i>, 5<\/b>, 91\u2013103 (2010).","DOI":"10.1021\/cb900271r"},{"key":"2","unstructured":"2) Ulaszewska MM, Trost K, Stanstrup J, Tuohy KM, Franceschi P, Chong M-F-F, George T, Minihane AM, Lovegrove JA, Mattivi F. Urinary metabolomic profiling to identify biomarkers of a flavonoid-rich and flavonoid-poor fruits and vegetables diet in adults: the FLAVURS trial. Metabolomics<\/i>, 12<\/b>, 32 (2016)."},{"key":"3","doi-asserted-by":"crossref","unstructured":"3) Nishiumi S, Kobayashi T, Ikeda A, Yoshie T, Kibi M, Izumi Y, Okuno T, Hayashi N, Kawano S, Takenawa T, Azuma T, Yoshida M. A novel serum metabolomics-based diagnostic approach for colorectal cancer. PLOS ONE<\/i>, 7<\/b>, e40459 (2012).","DOI":"10.1371\/journal.pone.0040459"},{"key":"4","unstructured":"4) Yuliana ND, Khatib A, Verpoorte R, Choi YH. Comprehensive extraction method integrated with NMR metabolomics: a new bioactivity screening method for plants, adenosine A1 receptor binding compounds in Orthosiphon stamineus<\/i> Benth. Anal. Chem.<\/i>, 83<\/b>, 6902\u20136906 (2011)."},{"key":"5","doi-asserted-by":"crossref","unstructured":"5) Song Q, Chen H, Li Y, Zhou H, Han Q, Diao X. Toxicological effects of benzo(\u03b1)pyrene, DDT and their mixture on the green mussel Perna viridis<\/i> revealed by proteomic and metabolomics approaches. Chemosphere<\/i>, 144<\/b>, 214\u2013224 (2016).","DOI":"10.1016\/j.chemosphere.2015.08.029"},{"key":"6","doi-asserted-by":"crossref","unstructured":"6) Takahashi K, Kohno H. Different polar metabolites and protein profiles between high- and low-quality Japanese ginjo<\/i> sake. PLOS ONE<\/i>, 11<\/b>, e0150524 (2016).","DOI":"10.1371\/journal.pone.0150524"},{"key":"7","doi-asserted-by":"crossref","unstructured":"7) Inoue K, Tanada C, Sakamoto T, Tsutsui H, Akiba T, Min JZ, Todoroki K, Yamano Y, Toyo\u2019oka T. Metabolomics approach of infant formula for the evaluation of contamination and degradation using hydrophilic interaction liquid chromatography coupled with mass spectrometry. Food Chem.<\/i>, 181<\/b>, 318\u2013324 (2015).","DOI":"10.1016\/j.foodchem.2015.02.117"},{"key":"8","doi-asserted-by":"crossref","unstructured":"8) Noguchi Y, Zhang QW, Sugimoto T, Furuhata Y, Sakai Y, Mori M, Takahashi M, Kimura T. Network analysis of plasma and tissue amino acids and the generation of an amino index for potential diagnostic use. Am. J. Clin. Nutr.<\/i>, 83<\/b>, 513S\u2013519S (2006).","DOI":"10.1093\/ajcn\/83.2.513S"},{"key":"9","doi-asserted-by":"crossref","unstructured":"9) Zhang Q, Takahashi M, Noguchi Y, Sugimoto T, Kimura T, Okumura A, Ishikawa T, Kakumu S. Plasma amino acid profiles applied for diagnosis of advanced liver fibrosis in patients with chronic hepatitis C infection. Hepatol. Res.<\/i>, 34<\/b>, 170\u2013177 (2006).","DOI":"10.1016\/j.hepres.2005.12.006"},{"key":"10","doi-asserted-by":"crossref","unstructured":"10) Kimura T, Hamase K, Miyoshi Y, Yamamoto R, Yasuda K, Mita M, Rakugi H, Hayashi T, Isaka Y. Chiral amino acid metabolomics for novel biomarker screening in the prognosis of chronic kidney disease. Sci. Rep.<\/i>, 6<\/b>, 26137 (2016).","DOI":"10.1038\/srep26137"},{"key":"11","doi-asserted-by":"crossref","unstructured":"11) Kal\u00edkov\u00e1 K, \u0160lechtov\u00e1 T, Tesa\u0159ov\u00e1 E. Enantiomeric ratio of amino acids as a tool for determination of aging and disease diagnostics by chromatographic measurement. Separations<\/i>, 3<\/b>, 30 (2016).","DOI":"10.3390\/separations3040030"},{"key":"12","unstructured":"12) Mochizuki T, Takayama T, Todoroki K, Inoue K, Min JZ, Toyo\u2019oka T. Towards the chiral metabolomics: liquid chromatography-mass spectrometry based DL-amino acid analysis after labeling with a new chiral reagent, (S<\/i>)-2,5-dioxopyrrolidin-1-yl-1-(4,6-dimethoxy-1,3,5-triazin-2-yl)pyrrolidine-2-carboxylate, and the application to saliva of healthy volunteers. Anal. Chim. Acta<\/i>, 875<\/b>, 73\u201382 (2015)."},{"key":"13","doi-asserted-by":"crossref","unstructured":"13) Miyagi Y, Higashiyama M, Gochi A, Akaike M, Ishikawa T, Miura T, Saruki N, Bando E, Kimura H, Imamura F, Moriyama M, Ikeda I, Chiba A, Oshita F, Imaizumi A, Yamamoto H, Miyano H, Horimoto K, Tochikubo O, Mitsushima T, Yamakado M, Okamoto N. Plasma free amino acid profiling of five types of cancer patients and its application for early detection. PLoS ONE<\/i>, 6<\/b>, e24143 (2011).","DOI":"10.1371\/journal.pone.0024143"},{"key":"14","doi-asserted-by":"crossref","unstructured":"14) Simi\u0144ska E, Koba M. Amino acid profiling as a method of discovering biomarkers for early diagnosis of cancer. Amino Acids<\/i>, 48<\/b>, 1339\u20131345 (2016).","DOI":"10.1007\/s00726-016-2215-2"},{"key":"15","doi-asserted-by":"crossref","unstructured":"15) Tomita R, Todoroki K, Machida K, Nishida S, Maruoka H, Yoshida H, Fujioka T, Nakashima M, Yamaguchi M, Nohta H. Assessment of the efficacy of anticancer drugs by amino acid metabolomics using fluorescence derivatization-HPLC. Anal. Sci.<\/i>, 30<\/b>, 751\u2013758 (2014).","DOI":"10.2116\/analsci.30.751"},{"key":"16","unstructured":"16) Tomita R, Todoroki K, Maruoka H, Yoshida H, Fujioka T, Nakashima M, Yamaguchi M, Nohta H. Amino acid metabolomics using LC-MS\/MS: Assessment of cancer-cell resistance in a simulated tumor microenvironment. Anal. Sci.<\/i>, 32<\/b>, 893\u2013900 (2016)."},{"key":"17","doi-asserted-by":"crossref","unstructured":"17) Onozuka H, Tsuchihara K, Esumi H. Hypoglycemic\/hypoxic condition in vitro<\/i> mimicking the tumor microenvironment markedly reduced the efficacy of anticancer drugs. Cancer Sci.<\/i>, 102<\/b>, 975\u2013982 (2011).","DOI":"10.1111\/j.1349-7006.2011.01880.x"},{"key":"18","unstructured":"18) Grasso C, Jansen G, Giovannetti E. Drug resistance in pancreatic cancer: impact of altered energy metabolism. Crit. Rev. Oncol. Hematol.<\/i>, 114<\/b>, 139\u2013152 (2017)."},{"key":"19","doi-asserted-by":"crossref","unstructured":"19) Valenzuela MMA, Neidigh JW, Wall NR. Antimetabolite treatment for pancreatic cancer. Chemotherapy<\/i>, 3<\/b>, 137 (2014). doi: 10.4172\/2167-7700.1000137","DOI":"10.4172\/2167-7700.1000137"},{"key":"20","doi-asserted-by":"crossref","unstructured":"20) Heinemann V, Xu Y-Z, Chubb S, Sen A, Hertel LW, Grindey GB, Plunkett W. Inhibition of ribonucleotide reduction in CCRF-CEM cells by 2\u2032,2\u2032-difluorodeoxycytidine. Mol. Pharmacol.<\/i>, 38<\/b>, 567\u2013572 (1990).","DOI":"10.1016\/S0026-895X(25)09518-5"},{"key":"21","doi-asserted-by":"crossref","unstructured":"21) Tomitsuka E, Kita K, Esumi H. The NADH-fumarate reductase system, a novel mitochondrial energy metabolism, is a new target for anticancer therapy in tumor microenvironments. Ann. N.Y. Acad. Sci.<\/i>, 1201<\/b>, 44\u201349 (2010).","DOI":"10.1111\/j.1749-6632.2010.05620.x"},{"key":"22","doi-asserted-by":"crossref","unstructured":"22) Esumi H, Lu J, Kurashima Y, Hanaoka T. Antitumor activity of pyrvinium pamoate, 6-(dimethylamino)-2-[2-(2,5-dimethyl-1-phenyl-1H<\/i>-pyrrol-3-yl)ethenyl]-1-methyl-quinolinium pamoate salt, showing preferential cytotoxicity during glucose starvation. Cancer Sci.<\/i>, 95<\/b>, 685\u2013690 (2004).","DOI":"10.1111\/j.1349-7006.2004.tb03330.x"},{"key":"23","doi-asserted-by":"crossref","unstructured":"23) Tomitsuka E, Kita K, Esumi H. An anticancer agent, pyrvinium pamoate inhibits the NADH-fumarate reductase system\u2014a unique mitochondrial energy metabolism in tumor microenvironments. J. Biochem.<\/i>, 152<\/b>, 171\u2013183 (2012).","DOI":"10.1093\/jb\/mvs041"},{"key":"24","doi-asserted-by":"crossref","unstructured":"24) Ishii I, Harada Y, Kasahara T. Reprofiling a classical anthelmintic, pyrvinium pamoate, as an anti-cancer drug targeting mitochondrial respiration. Front. Oncol.<\/i>, 2<\/b>, 137 (2012).","DOI":"10.3389\/fonc.2012.00137"},{"key":"25","doi-asserted-by":"crossref","unstructured":"25) Ishiyama M, Miyazono Y, Sasamoto K, Ohkura Y, Ueno K. A highly water-soluble disulfonated tetrazolium salt as a chromogenic indicator for NADH as well as cell viability. Talanta<\/i>, 44<\/b>, 1299\u20131305 (1997).","DOI":"10.1016\/S0039-9140(97)00017-9"},{"key":"26","doi-asserted-by":"crossref","unstructured":"26) Daga RR, Bola\u00f1os P, Moreno S. Regulated mRNA stability of the Cdk inhibitor Rum1 links nutrient status to cell cycle progression. Curr. Biol.<\/i>, 13<\/b>, 2015\u20132024 (2003).","DOI":"10.1016\/j.cub.2003.10.061"},{"key":"27","doi-asserted-by":"crossref","unstructured":"27) Gabai VL, Zamulaeva IV, Mosin AF, Makarova YM, Mosina VA, Budagova KR, Malutina YV, Kabakov AE. Resistance of Ehrlich tumor cells to apoptosis can be due to accumulation of heat shock proteins. FEBS Lett.<\/i>, 375<\/b>, 21\u201326 (1995).","DOI":"10.1016\/0014-5793(95)01152-5"},{"key":"28","unstructured":"28) Akakura N, Kobayashi M, Horiuchi I, Suzuki A, Wang J, Chen J, Niizeki H, Kawamura K, Hosokawa M, Asaka M. Constitutive expression of hypoxia-inducible factor-1alpha renders pancreatic cancer cells resistant to apoptosis induced by hypoxia and nutrient deprivation. Cancer Res.<\/i>, 61<\/b>, 6548\u20136554 (2001)."},{"key":"29","doi-asserted-by":"crossref","unstructured":"29) Fukutake N, Ueno M, Hiraoka N, Shimada K, Shiraishi K, Saruki N, Ito T, Yamakado M, Ono N, Imaizumi A, Kikuchi S, Yamamoto H, Katayama K. A novel multivariate index for pancreatic cancer detection based on the plasma free amino acid profile. PLOS ONE<\/i>, 10<\/b>, e0132223 (2015).","DOI":"10.1371\/journal.pone.0132223"},{"key":"30","doi-asserted-by":"crossref","unstructured":"30) Nishiumi S, Shinohara M, Ikeda A, Yoshie T, Hatano N, Kakuyama S, Mizuno S, Sanuki T, Kutsumi H, Fukusaki E, Azuma T, Takenawa T, Yoshida M. Serum metabolomics as a novel diagnostic approach for pancreatic cancer. Metabolomics<\/i>, 6<\/b>, 518\u2013528 (2010).","DOI":"10.1007\/s11306-010-0224-9"},{"key":"31","doi-asserted-by":"crossref","unstructured":"31) Warburg O. On the origin of cancer cells. Science<\/i>, 123<\/b>, 309\u2013314 (1956).","DOI":"10.1126\/science.123.3191.309"},{"key":"32","unstructured":"32) DeBerardinis RJ, Mancuso A, Daikhin E, Nissim I, Yudkoff M, Wehrli S, Thompson CB. Beyond aerobic glycolysis: transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis. Proc. Natl. Acad. Sci. U.S.A.<\/i>, 104<\/b>, 19345\u201319350 (2007)."},{"key":"33","doi-asserted-by":"crossref","unstructured":"33) Hirayama A, Kami K, Sugimoto M, Sugawara M, Toki N, Onozuka H, Kinoshita T, Saito N, Ochiai A, Tomita M, Esumi H, Soga T. Quantitative metabolome profiling of colon and stomach cancer microenvironment by capillary electrophoresis time-of-flight mass spectrometry. Cancer Res.<\/i>, 69<\/b>, 4918\u20134925 (2009).","DOI":"10.1158\/0008-5472.CAN-08-4806"},{"key":"34","doi-asserted-by":"crossref","unstructured":"34) Zhang J, Liu L, Wei S, Nagana Gowda GA, Hammoud Z, Kesler KA, Raftery D. Metabolomics study of esophageal adenocarcinoma. J. Thorac. Cardiovasc. Surg.<\/i>, 141<\/b>, 469\u2013475, 475.e1\u2013475.e4 (2011).","DOI":"10.1016\/j.jtcvs.2010.08.025"},{"key":"35","doi-asserted-by":"crossref","unstructured":"35) Sato K, Tsuchihara K, Fujii S, Sugiyama M, Goya T, Atomi Y, Ueno T, Ochiai A, Esumi H. Autophagy is activated in colorectal cancer cells and contributes to the tolerance to nutrient deprivation. Cancer Res.<\/i>, 67<\/b>, 9677\u20139684 (2007).","DOI":"10.1158\/0008-5472.CAN-07-1462"},{"key":"36","doi-asserted-by":"crossref","unstructured":"36) Hashimoto D, Bl\u00e4uer M, Hirota M, Ikonen NH, Sand J, Laukkarinen J. Autophagy is needed for the growth of pancreatic adenocarcinoma and has a cytoprotective effect against anticancer drugs. Eur. J. Cancer<\/i>, 50<\/b>, 1382\u20131390 (2014).","DOI":"10.1016\/j.ejca.2014.01.011"},{"key":"37","unstructured":"37) Kami K, Tomitsuka E, Tomita M, Kita K, Esumi H, Soga T. Elucidation of energy metabolism of cancer microenvironment by metabolome analysis. Experimental medicine Extra<\/i>. (Esumi H, Takakura N, Miyazono K, Mori M. ed.) Vol. 27, Yodosha, Tokyo, Japan, pp. 215\u2013221 (2009)."},{"key":"38","doi-asserted-by":"crossref","unstructured":"38) Ueda J-Y, Athikomkulchai S, Miyatake R, Saiki I, Esumi H, Awale S. (+)-Grandifloracin, an antiausterity agent, induces autophagic PANC-1 pancreatic cancer cell death. Drug Des. Devel. Ther.<\/i>, 8<\/b>, 39\u201347 (2013).","DOI":"10.2147\/DDDT.S52168"},{"key":"39","doi-asserted-by":"crossref","unstructured":"39) Lu J, Kunimoto S, Yamazaki Y, Kaminishi M, Esumi H. Kigamicin D, a novel anticancer agent based on a new anti-austerity strategy targeting cancer cells\u2019 tolerance to nutrient starvation. Cancer Sci.<\/i>, 95<\/b>, 547\u2013552 (2004).","DOI":"10.1111\/j.1349-7006.2004.tb03247.x"},{"key":"40","doi-asserted-by":"crossref","unstructured":"40) Awale S, Lu J, Kalauni SK, Kurashima Y, Tezuka Y, Kadota S, Esumi H. Identification of arctigenin as an antitumor agent having the ability to eliminate the tolerance of cancer cells to nutrient starvation. Cancer Res.<\/i>, 66<\/b>, 1751\u20131757 (2006).","DOI":"10.1158\/0008-5472.CAN-05-3143"},{"key":"41","unstructured":"41) Peters KB, Brown JM. Tirapazamine: a hypoxia-activated topoisomerase II poison. Cancer Res.<\/i>, 62<\/b>, 5248\u20135253 (2002)."}],"container-title":["Biological and Pharmaceutical Bulletin"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/bpb\/41\/2\/41_b17-00746\/_pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T10:48:40Z","timestamp":1751280520000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/bpb\/41\/2\/41_b17-00746\/_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018]]},"references-count":41,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2018]]}},"URL":"https:\/\/doi.org\/10.1248\/bpb.b17-00746","relation":{},"ISSN":["0918-6158","1347-5215"],"issn-type":[{"type":"print","value":"0918-6158"},{"type":"electronic","value":"1347-5215"}],"subject":[],"published":{"date-parts":[[2018]]}}}