{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T01:25:23Z","timestamp":1782955523222,"version":"3.54.5"},"reference-count":47,"publisher":"Portland Press Ltd.","issue":"10","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2016,5,15]]},"abstract":"<jats:p>Polyamine metabolism is an attractive anticancer drug target, since polyamines are absolutely required for cellular proliferation, and increased levels of polyamines and their biosynthetic enzyme ornithine decarboxylase (ODC) are associated with cancer. Triethylenetetramine (TETA) is a charge-deficient isosteric analogue of the polyamine spermidine (Spd) and a Cu(II)-chelating compound used for the treatment of Wilson's disease, and it has been implicated as a potential anticancer therapeutic drug. In the present study, we studied the effects of TETA in comparison with two other Cu(II)-chelators, D-penicillamine (PA) and tetrathiomolybdate (TTM), on polyamine metabolism in DU145 prostate carcinoma, MCF-7 breast carcinoma and JEG-3 choriocarcinoma cells. TETA induced antizyme, down-regulated ODC and inhibited [14C] Spd uptake. Moreover, it completely prevented \u03b1-difluoromethylornithine (DFMO)-induced increase in [14C] Spd uptake, and inhibited [14C] putrescine (Put) uptake and ODC activity in\u00a0vivo. Seven-day treatment of DU145 cells with TETA caused growth cessation by reducing intracellular polyamine levels and suppressing the formation of hypusinated eukaryotic translation initiation factor 5A (eIF5A). TETA or its N-acetylated metabolites also inhibited spermine (Spm), diamine and semicarbazide-sensitive amine oxidases and decreased the level of intracellular reactive oxygen species. Moreover, TETA inhibited the utilization of Put as energy source via the tricarboxylic acid (TCA) cycle, as indicated by decreased production of 14CO2 from [14C] Put. These results indicate that TETA attacks multiple proven anticancer drug targets not attributed to copper chelation, which warrants further studies to reveal its potential in cancer chemoprevention and cure.<\/jats:p>","DOI":"10.1042\/bcj20160134","type":"journal-article","created":{"date-parts":[[2016,3,22]],"date-time":"2016-03-22T02:04:50Z","timestamp":1458612290000},"page":"1433-1441","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Triethylenetetramine modulates polyamine and energy metabolism and inhibits cancer cell proliferation"],"prefix":"10.1042","volume":"473","author":[{"given":"Mervi\u00a0T.","family":"Hyv\u00f6nen","sequence":"first","affiliation":[{"name":"School of Pharmacy, University of Eastern Finland, Yliopistonranta 1C, 70210 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebahat","family":"Ucal","sequence":"additional","affiliation":[{"name":"School of Pharmacy, University of Eastern Finland, Yliopistonranta 1C, 70210 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markku","family":"Pasanen","sequence":"additional","affiliation":[{"name":"School of Pharmacy, University of Eastern Finland, Yliopistonranta 1C, 70210 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sirpa","family":"Per\u00e4niemi","sequence":"additional","affiliation":[{"name":"School of Pharmacy, University of Eastern Finland, Yliopistonranta 1C, 70210 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janne","family":"Weisell","sequence":"additional","affiliation":[{"name":"School of Pharmacy, University of Eastern Finland, Yliopistonranta 1C, 70210 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maxim","family":"Khomutov","sequence":"additional","affiliation":[{"name":"Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov St 32, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex\u00a0R.","family":"Khomutov","sequence":"additional","affiliation":[{"name":"Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov St 32, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jouko","family":"Veps\u00e4l\u00e4inen","sequence":"additional","affiliation":[{"name":"School of Pharmacy, University of Eastern Finland, Yliopistonranta 1C, 70210 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leena","family":"Alhonen","sequence":"additional","affiliation":[{"name":"School of Pharmacy, University of Eastern Finland, Yliopistonranta 1C, 70210 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuomo\u00a0A.","family":"Kein\u00e4nen","sequence":"additional","affiliation":[{"name":"School of Pharmacy, University of Eastern Finland, Yliopistonranta 1C, 70210 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2016,5,11]]},"reference":[{"key":"2021112216272715700_B1","doi-asserted-by":"publisher","first-page":"880","DOI":"10.1002\/iub.230","article-title":"Mammalian polyamine metabolism and function","volume":"61","author":"Pegg","year":"2009","journal-title":"IUBMB Life"},{"key":"2021112216272715700_B2","doi-asserted-by":"publisher","first-page":"e3","DOI":"10.1017\/erm.2013.3","article-title":"Polyamines and cancer: implications for chemotherapy and chemoprevention","volume":"15","author":"Nowotarski","year":"2013","journal-title":"Expert Rev. 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