{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T14:10:08Z","timestamp":1787062208126,"version":"build-2736575974"},"reference-count":42,"publisher":"World Scientific Pub Co Pte Ltd","issue":"03","funder":[{"DOI":"10.13039\/501100006606","name":"Tianjin Natural Science Foundation","doi-asserted-by":"crossref","award":["20JCZDJC00780"],"award-info":[{"award-number":["20JCZDJC00780"]}],"id":[{"id":"10.13039\/501100006606","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Am. J. Chin. Med."],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:p>Hypoxia-inducible factor-1 (HIF-1) is an [Formula: see text]\/[Formula: see text] heterodimeric transcription factor. In normal mammalian cells, HIF-1[Formula: see text] is hydroxylated and degraded upon biosynthesis. However, HIF-1[Formula: see text] is frequently expressed in cancer and adds to cancer malignancy. In this study, we investigated whether green tea-derived epigallocatechin-3-gallate (EGCG) decreased HIF-1[Formula: see text] in pancreatic cancer cells. After MiaPaCa-2 and PANC-1 pancreatic cancer cells were exposed to EGCG in vitro, we performed a Western blot to determine native and hydroxylated HIF-1[Formula: see text], which was in turn used to assess HIF-1[Formula: see text] production. In order to assess HIF-1[Formula: see text] stability, we determined the HIF-1[Formula: see text] after MiaPaCa-2 and PANC-1 cells were switched from hypoxia to normoxia. We found that EGCG decreased both production and stability of HIF-1[Formula: see text]. Further, the EGCG-induced decrease in HIF-1[Formula: see text] reduced intracellular glucose transporter-1 and glycolytic enzymes and attenuated glycolysis, ATP production, and cell growth. Because EGCG is known to inhibit cancer-induced insulin receptor (IR) and insulin-like growth factor-1 receptor (IGF1R), we created three MiaPaCa-2 sublines whose IR, IGF1R, and HIF-1[Formula: see text] were decreased using RNA interference. From wild-type MiaPaCa-2 cells and these sublines, we found evidence that suggested that the EGCG-induced inhibition of HIF-1[Formula: see text] was both dependent on and independent of IR and IGF1R. In vivo, we transplanted wild-type MiaPaCa-2 cells in athymic mice and treated the mice with EGCG or vehicle. When the resulting tumors were analyzed, we found that EGCG decreased tumor-induced HIF-1[Formula: see text] and tumor growth. In conclusion, EGCG decreased HIF-1[Formula: see text] in pancreatic cancer cells and sabotaged the cells. The anticancer effects of EGCG were both dependent on and independent of IR and IGF1R.<\/jats:p>","DOI":"10.1142\/s0192415x23500362","type":"journal-article","created":{"date-parts":[[2023,3,3]],"date-time":"2023-03-03T10:04:37Z","timestamp":1677837877000},"page":"761-777","source":"Crossref","is-referenced-by-count":10,"title":["Epigallocatechin-3-Gallate Decreases Hypoxia-Inducible Factor-1 in Pancreatic Cancer Cells"],"prefix":"10.1142","volume":"51","author":[{"given":"Lijuan","family":"Hu","sequence":"first","affiliation":[{"name":"The Laboratory of Acute Abdomen Disease, Associated Organ Injury and Repair, Nankai Hospital Affiliated to Tianjin Medical University, Tianjin 300100, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqing","family":"Xu","sequence":"additional","affiliation":[{"name":"The Graduate School, Tianjin Medical University, Tianjin 300070, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xijuan","family":"Chen","sequence":"additional","affiliation":[{"name":"The Graduate School, Tianjin Medical University, Tianjin 300070, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Qiu","sequence":"additional","affiliation":[{"name":"The Graduate School, Tianjin Medical University, Tianjin 300070, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuju","family":"Li","sequence":"additional","affiliation":[{"name":"The Graduate School, Tianjin Medical University, Tianjin 300070, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dapeng","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Laboratory of Acute Abdomen Disease, Associated Organ Injury and Repair, Nankai Hospital Affiliated to Tianjin Medical University, Tianjin 300100, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Wang","sequence":"additional","affiliation":[{"name":"The Laboratory of Acute Abdomen Disease, Associated Organ Injury and Repair, Nankai Hospital Affiliated to Tianjin Medical University, Tianjin 300100, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"219","published-online":{"date-parts":[[2023,3,3]]},"reference":[{"key":"S0192415X23500362BIB001","doi-asserted-by":"crossref","first-page":"245","DOI":"10.2174\/1568009611313030003","volume":"13","author":"Agani F.","year":"2013","journal-title":"Curr. Cancer Drug Targets"},{"key":"S0192415X23500362BIB002","doi-asserted-by":"crossref","first-page":"1404","DOI":"10.1002\/med.21477","volume":"38","author":"Bhattarai D.","year":"2018","journal-title":"Med. Res. Rev."},{"key":"S0192415X23500362BIB003","doi-asserted-by":"crossref","first-page":"555","DOI":"10.3390\/ijms22020555","volume":"22","author":"Cao J.","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"S0192415X23500362BIB004","first-page":"155","volume":"23","author":"Fu J.D.","year":"2019","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"S0192415X23500362BIB005","doi-asserted-by":"crossref","first-page":"38205","DOI":"10.1074\/jbc.M203781200","volume":"277","author":"Fukuda R.","year":"2002","journal-title":"J. Biol. Chem."},{"key":"S0192415X23500362BIB006","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1080\/10408398.2016.1231168","volume":"58","author":"Gan R.Y.","year":"2018","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"S0192415X23500362BIB007","first-page":"354143","volume":"2015","author":"Gao J.L.","year":"2015","journal-title":"Biomed. Res. Int."},{"key":"S0192415X23500362BIB008","first-page":"4557","volume":"22","author":"Gu J.J.","year":"2018","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"S0192415X23500362BIB009","doi-asserted-by":"crossref","first-page":"88008","DOI":"10.18632\/oncotarget.21330","volume":"8","author":"Hu L.","year":"2017","journal-title":"Oncotarget"},{"key":"S0192415X23500362BIB010","doi-asserted-by":"publisher","DOI":"10.1142\/S0192415X20500482"},{"key":"S0192415X23500362BIB011","first-page":"e21826","volume":"35","author":"Hu L.","year":"2021","journal-title":"FASEB J."},{"key":"S0192415X23500362BIB012","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.1158\/1535-7163.MCT-09-0604","volume":"9","author":"Kang H.G.","year":"2010","journal-title":"Mol. Cancer Ther."},{"key":"S0192415X23500362BIB013","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1016\/S0360-3016(00)00803-8","volume":"48","author":"Koong A.C.","year":"2000","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"S0192415X23500362BIB014","doi-asserted-by":"crossref","first-page":"28479","DOI":"10.1038\/srep28479","volume":"6","author":"Li S.","year":"2016","journal-title":"Sci. Rep."},{"key":"S0192415X23500362BIB015","doi-asserted-by":"crossref","first-page":"5947","DOI":"10.1158\/1078-0432.CCR-18-4145","volume":"25","author":"Li Z.","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"S0192415X23500362BIB016","doi-asserted-by":"publisher","DOI":"10.1142\/S0192415X13500444"},{"key":"S0192415X23500362BIB017","first-page":"435","volume":"19","author":"Luo H.Q.","year":"2014","journal-title":"J. BUON"},{"key":"S0192415X23500362BIB018","doi-asserted-by":"publisher","DOI":"10.1142\/S0192415X16500555"},{"key":"S0192415X23500362BIB019","doi-asserted-by":"crossref","first-page":"238","DOI":"10.3390\/ijms20020238","volume":"20","author":"Nagao A.","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"S0192415X23500362BIB020","doi-asserted-by":"crossref","first-page":"27382","DOI":"10.1038\/srep27382","volume":"6","author":"Oh E.T.","year":"2016","journal-title":"Sci. Rep."},{"key":"S0192415X23500362BIB021","doi-asserted-by":"crossref","first-page":"3415","DOI":"10.7150\/thno.20861","volume":"7","author":"Oh E.T.","year":"2017","journal-title":"Theranostics"},{"key":"S0192415X23500362BIB022","doi-asserted-by":"publisher","DOI":"10.1142\/S0192415X22500240"},{"key":"S0192415X23500362BIB023","doi-asserted-by":"crossref","first-page":"22642","DOI":"10.1074\/jbc.272.36.22642","volume":"272","author":"Salceda S.","year":"1997","journal-title":"J. Biol. Chem."},{"key":"S0192415X23500362BIB024","first-page":"5447","volume":"12","author":"Semenza G.L.","year":"1992","journal-title":"Mol. Cell. Biol."},{"key":"S0192415X23500362BIB025","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.3390\/antiox10071076","volume":"10","author":"Tang G.","year":"2021","journal-title":"Antioxidants (Basel)"},{"key":"S0192415X23500362BIB026","doi-asserted-by":"crossref","first-page":"R67","DOI":"10.1530\/JME-12-0259","volume":"50","author":"Trajkovic-Arsic M.","year":"2013","journal-title":"J. Mol. Endocrinol."},{"key":"S0192415X23500362BIB027","doi-asserted-by":"crossref","first-page":"F63","DOI":"10.1530\/ERC-12-0026","volume":"19","author":"Varewijck A.J.","year":"2012","journal-title":"Endocr. Relat. Cancer"},{"key":"S0192415X23500362BIB028","doi-asserted-by":"crossref","first-page":"9103","DOI":"10.1038\/s41598-021-88478-z","volume":"11","author":"Via F.I.D.","year":"2021","journal-title":"Sci. Rep."},{"key":"S0192415X23500362BIB029","first-page":"290516","volume":"2010","author":"Vu H.A.","year":"2010","journal-title":"J. Biomed. Biotechnol."},{"key":"S0192415X23500362BIB030","doi-asserted-by":"crossref","first-page":"469","DOI":"10.2353\/ajpath.2007.060489","volume":"170","author":"Wang F.","year":"2007","journal-title":"Am. J. Pathol."},{"key":"S0192415X23500362BIB031","first-page":"873175","volume":"2012","author":"Wang Z.","year":"2012","journal-title":"Evid. Based Complement. Alternat. Med."},{"key":"S0192415X23500362BIB032","doi-asserted-by":"publisher","DOI":"10.1142\/S0192415X14500803"},{"key":"S0192415X23500362BIB033","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1186\/s12885-018-4271-3","volume":"18","author":"Wang F.","year":"2018","journal-title":"BMC Cancer"},{"key":"S0192415X23500362BIB034","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1085\/jgp.8.6.519","volume":"8","author":"Warburg O.","year":"1927","journal-title":"J. Gen. Physiol."},{"key":"S0192415X23500362BIB035","doi-asserted-by":"crossref","first-page":"5682","DOI":"10.1039\/C8FO01397G","volume":"9","author":"Wei R.","year":"2018","journal-title":"Food Funct."},{"key":"S0192415X23500362BIB036","doi-asserted-by":"crossref","first-page":"1856","DOI":"10.3390\/nu11081856","volume":"11","author":"Wei R.","year":"2019","journal-title":"Nutrients"},{"key":"S0192415X23500362BIB037","doi-asserted-by":"crossref","first-page":"108546","DOI":"10.1016\/j.abb.2020.108546","volume":"692","author":"Wei R.","year":"2020","journal-title":"Arch. Biochem. Biophys."},{"key":"S0192415X23500362BIB038","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1002\/pros.23448","volume":"78","author":"Xiao H.","year":"2018","journal-title":"Prostate"},{"key":"S0192415X23500362BIB039","doi-asserted-by":"crossref","first-page":"575","DOI":"10.3892\/mmr.2021.12214","volume":"24","author":"Xu Y.","year":"2021","journal-title":"Mol. Med. Rep."},{"key":"S0192415X23500362BIB040","doi-asserted-by":"crossref","first-page":"1460","DOI":"10.3390\/cancers11101460","volume":"11","author":"Yan L.","year":"2019","journal-title":"Cancers (Basel)"},{"key":"S0192415X23500362BIB041","doi-asserted-by":"publisher","DOI":"10.1142\/S0192415X19500356"},{"key":"S0192415X23500362BIB042","first-page":"5830","volume":"59","author":"Zhong H.","year":"1999","journal-title":"Cancer Res."}],"container-title":["The American Journal of Chinese Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.worldscientific.com\/doi\/pdf\/10.1142\/S0192415X23500362","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,30]],"date-time":"2023-05-30T05:07:07Z","timestamp":1685423227000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.worldscientific.com\/doi\/10.1142\/S0192415X23500362"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1]]},"references-count":42,"journal-issue":{"issue":"03","published-print":{"date-parts":[[2023,1]]}},"alternative-id":["10.1142\/S0192415X23500362"],"URL":"https:\/\/doi.org\/10.1142\/s0192415x23500362","relation":{},"ISSN":["0192-415X","1793-6853"],"issn-type":[{"value":"0192-415X","type":"print"},{"value":"1793-6853","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1]]}}}