{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T15:37:32Z","timestamp":1772552252793,"version":"3.50.1"},"reference-count":50,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Toxicology and Applied Pharmacology"],"published-print":{"date-parts":[[2025,4]]},"DOI":"10.1016\/j.taap.2025.117259","type":"journal-article","created":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T00:09:33Z","timestamp":1738714173000},"page":"117259","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":2,"special_numbering":"C","title":["Effects of hypoxia and iron on ascorbic acid-mediated cytotoxicity in prostate cancer cell lines"],"prefix":"10.1016","volume":"497","author":[{"given":"Samiksha","family":"Deme","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ida","family":"Ramezani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan","family":"Coulter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Channing","family":"Paller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph","family":"Bressler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.taap.2025.117259_bb0005","series-title":"Cancer Chemotherapy, in: StatPearls","author":"Amjad","year":"2024"},{"key":"10.1016\/j.taap.2025.117259_bb0010","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1093\/carcin\/18.6.1215","article-title":"Androgen responsive adult human prostatic epithelial cell lines immortalized by human papillomavirus 18","volume":"18","author":"Bello","year":"1997","journal-title":"Carcinogenesis"},{"key":"10.1016\/j.taap.2025.117259_bb0015","doi-asserted-by":"crossref","first-page":"4223","DOI":"10.1093\/nar\/27.21.4223","article-title":"HIF-1-mediated activation of transferrin receptor gene transcription by iron chelation","volume":"27","author":"Bianchi","year":"1999","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.taap.2025.117259_bb0020","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1074\/jbc.M603761200","article-title":"Specific aquaporins facilitate the diffusion of hydrogen peroxide across membranes","volume":"282","author":"Bienert","year":"2007","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.taap.2025.117259_bb0025","doi-asserted-by":"crossref","first-page":"13604","DOI":"10.1073\/pnas.0506390102","article-title":"Pharmacologic ascorbic acid concentrations selectively kill cancer cells: action as a pro-drug to deliver hydrogen peroxide to tissues","volume":"102","author":"Chen","year":"2005","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.taap.2025.117259_bb0030","doi-asserted-by":"crossref","first-page":"9092","DOI":"10.1074\/jbc.M112.436790","article-title":"Intestinal dehydroascorbic acid (DHA) transport mediated by the facilitative sugar transporters, GLUT2 and GLUT8","volume":"288","author":"Corpe","year":"2013","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.taap.2025.117259_bb0035","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1186\/1476-4598-6-61","article-title":"Differential effects of hypoxia on etoposide-induced apoptosis according to the cancer cell lines","volume":"6","author":"Cosse","year":"2007","journal-title":"Mol. Cancer"},{"key":"10.1016\/j.taap.2025.117259_bb0040","first-page":"172","article-title":"Role of tumor hypoxia in acquisition of resistance to microtubule-stabilizing drugs","volume":"1855","author":"Das","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"10.1016\/j.taap.2025.117259_bb0045","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.biocel.2004.08.012","article-title":"Hypoxia-inducible factor 1: regulation by hypoxic and non-hypoxic activators","volume":"37","author":"D\u00e9ry","year":"2005","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"10.1016\/j.taap.2025.117259_bb0050","first-page":"443","article-title":"Ascorbic acid: chemistry, biology and the treatment of cancer","volume":"1826","author":"Du","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"10.1016\/j.taap.2025.117259_bb0055","doi-asserted-by":"crossref","DOI":"10.1016\/j.taap.2020.115354","article-title":"Ethyl maltol enhances copper mediated cytotoxicity in lung epithelial cells","volume":"410","author":"Durrani","year":"2021","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"10.1016\/j.taap.2025.117259_bb0060","doi-asserted-by":"crossref","first-page":"e190","DOI":"10.1038\/oncsis.2015.50","article-title":"Hypoxia and metabolic adaptation of cancer cells","volume":"5","author":"Eales","year":"2016","journal-title":"Oncogenesis"},{"key":"10.1016\/j.taap.2025.117259_bb0065","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3233\/DMA-2011-0805","article-title":"Expression of hypoxia inducible factor-1 alpha in matched hormone naive and castrate resistant prostate cancer specimens","volume":"8","author":"Elsberger","year":"2010","journal-title":"Cancer Biomark."},{"key":"10.1016\/j.taap.2025.117259_bb0070","first-page":"201","article-title":"Assessing the survival of mrc-5 and a549 cell lines upon exposure to ascorbic acid and sodium ascorbate - biomed 2011","volume":"47","author":"Farah","year":"2011","journal-title":"Biomed. Sci. Instrum."},{"key":"10.1016\/j.taap.2025.117259_bb0075","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1007\/BF02592403","article-title":"Taxol (paclitaxel): a novel anti-microtubule agent with remarkable anti-neoplastic activity","volume":"24","author":"Foa","year":"1994","journal-title":"Int. J. Clin. Lab. Res."},{"key":"10.1016\/j.taap.2025.117259_bb0080","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1007\/s00280-010-1418-6","article-title":"Ascorbate exerts anti-proliferative effects through cell cycle inhibition and sensitizes tumor cells towards cytostatic drugs","volume":"67","author":"Fr\u00f6mberg","year":"2011","journal-title":"Cancer Chemother. Pharmacol."},{"key":"10.1016\/j.taap.2025.117259_bb0085","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/S0090-4295(02)01583-2","article-title":"Chemotherapy for prostate cancer","volume":"60","author":"Gilligan","year":"2002","journal-title":"Urology"},{"key":"10.1016\/j.taap.2025.117259_bb0090","doi-asserted-by":"crossref","unstructured":"Gon\u00e7alves, A.C., Alves, V., Silva, T., Carvalho, C., Oliveira, C.R. de, Sarmento-Ribeiro, A.B., 2013. Oxidative stress mediates apoptotic effects of ascorbate and dehydroascorbate in human myelodysplasia cells in vitro. Toxicol. In Vitro 27, 1542\u20131549. doi: https:\/\/doi.org\/10.1016\/j.tiv.2013.03.009.","DOI":"10.1016\/j.tiv.2013.03.009"},{"key":"10.1016\/j.taap.2025.117259_bb0095","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1002\/pros.23276","article-title":"Low p16INK4a expression in early passage human prostate basal epithelial cells enables immortalization by telomerase expression alone","volume":"77","author":"Graham","year":"2017","journal-title":"Prostate"},{"key":"10.1016\/j.taap.2025.117259_bb0100","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1080\/02656736.2017.1354403","article-title":"An optimised spectrophotometric assay for convenient and accurate quantitation of intracellular iron from iron oxide nanoparticles","volume":"34","author":"Hedayati","year":"2018","journal-title":"Int. J. Hyperthermia"},{"key":"10.1016\/j.taap.2025.117259_bb0105","first-page":"4716","article-title":"Wild-type p53 suppresses growth of human prostate cancer cells containing mutant p53 alleles","volume":"51","author":"Isaacs","year":"1991","journal-title":"Cancer Res."},{"key":"10.1016\/j.taap.2025.117259_bb0110","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1101\/gad.12.2.149","article-title":"Cellular and developmental control of O2 homeostasis by hypoxia-inducible factor 1 alpha","volume":"12","author":"Iyer","year":"1998","journal-title":"Genes Dev."},{"key":"10.1016\/j.taap.2025.117259_bb0115","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/s11010-012-1504-7","article-title":"Androgen deprivation by flutamide modulates uPAR, MMP-9 expressions, lipid profile, and oxidative stress: amelioration by daidzein","volume":"374","author":"Lateef","year":"2013","journal-title":"Mol. Cell. Biochem."},{"key":"10.1016\/j.taap.2025.117259_bb0120","first-page":"103","article-title":"A flow cell assay for evaluation of whole cell drug efflux kinetics: analysis of paclitaxel efflux in CCRF-CEM leukemia cells overexpressing P-glycoprotein","volume":"29","author":"Lin","year":"2001","journal-title":"Drug Metab. Dispos."},{"key":"10.1016\/j.taap.2025.117259_bb0125","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1002\/pros.20483","article-title":"PC3, but not DU145, human prostate cancer cells retain the coregulators required for tumor suppressor ability of androgen receptor","volume":"66","author":"Litvinov","year":"2006","journal-title":"Prostate"},{"key":"10.1016\/j.taap.2025.117259_bb0130","doi-asserted-by":"crossref","first-page":"20130676","DOI":"10.1259\/bjr.20130676","article-title":"Defining normoxia, physoxia and hypoxia in tumours\u2014implications for treatment response","volume":"87","author":"McKeown","year":"2014","journal-title":"Br. J. Radiol."},{"key":"10.1016\/j.taap.2025.117259_bb0135","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1091\/mbc.e10-04-0335","article-title":"The proliferation rate paradox in antimitotic chemotherapy","volume":"23","author":"Mitchison","year":"2012","journal-title":"MBoC"},{"key":"10.1016\/j.taap.2025.117259_bb0140","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.redox.2013.11.005","article-title":"Pharmacological ascorbate and ionizing radiation (IR) increase labile iron in pancreatic cancer","volume":"2","author":"Moser","year":"2013","journal-title":"Redox Biol."},{"key":"10.1016\/j.taap.2025.117259_bb0145","doi-asserted-by":"crossref","first-page":"89","DOI":"10.3390\/antiox7070089","article-title":"Systematic review of intravenous ascorbate in cancer clinical trials","volume":"7","author":"Nauman","year":"2018","journal-title":"Antioxidants"},{"issue":"Pt 3","key":"10.1016\/j.taap.2025.117259_bb0150","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1042\/bj3150931","article-title":"Purification, cloning and expression of dehydroascorbic acid-reducing activity from human neutrophils: identification as glutaredoxin","volume":"315","author":"Park","year":"1996","journal-title":"Biochem. J."},{"key":"10.1016\/j.taap.2025.117259_bb0155","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1089\/15230860260196164","article-title":"Differential regulation of hydrogen peroxide and Fas-dependent apoptosis pathways by dehydroascorbate, the oxidized form of vitamin C","volume":"4","author":"Puskas","year":"2002","journal-title":"Antioxid. Redox Signal."},{"key":"10.1016\/j.taap.2025.117259_bb0160","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1007\/s00109-022-02273-5","article-title":"Mitochondrial respiration inhibitor enhances the anti-tumor effect of high-dose ascorbic acid in castration-resistant prostate cancer","volume":"101","author":"Qiu","year":"2023","journal-title":"J. Mol. Med."},{"key":"10.1016\/j.taap.2025.117259_bb0165","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0054251","article-title":"The role of hypoxia-inducible factor 1\u03b1 in determining the properties of castrate-resistant prostate cancers","volume":"8","author":"Ranasinghe","year":"2013","journal-title":"PloS One"},{"key":"10.1016\/j.taap.2025.117259_bb0170","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1002\/jso.2930460108","article-title":"Two prostate carcinoma cell lines demonstrate abnormalities in tumor suppressor genes","volume":"46","author":"Rubin","year":"1991","journal-title":"J. Surg. Oncol."},{"key":"10.1016\/j.taap.2025.117259_bb0175","doi-asserted-by":"crossref","first-page":"18982","DOI":"10.1074\/jbc.272.30.18982","article-title":"Glucose transporter isoforms GLUT1 and GLUT3 transport dehydroascorbic acid","volume":"272","author":"Rumsey","year":"1997","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.taap.2025.117259_bb0180","doi-asserted-by":"crossref","first-page":"3842","DOI":"10.3892\/mmr.2015.3217","article-title":"Resistance of SMMC-7721 hepatoma cells to etoposide in hypoxia is reversed by VEGF inhibitor","volume":"11","author":"Shi","year":"2015","journal-title":"Mol. Med. Rep."},{"key":"10.1016\/j.taap.2025.117259_bb0185","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1038\/onc.2009.322","article-title":"Castration resistance of prostate cancer cells caused by castration-induced oxidative stress through Twist1 and androgen receptor overexpression","volume":"29","author":"Shiota","year":"2010","journal-title":"Oncogene"},{"key":"10.1016\/j.taap.2025.117259_bb0190","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1111\/jcmm.12207","article-title":"The ROS-induced cytotoxicity of ascorbate is attenuated by hypoxia and HIF-1alpha in the NCI60 cancer cell lines","volume":"18","author":"Sinnberg","year":"2014","journal-title":"J. Cell. Mol. Med."},{"key":"10.1016\/j.taap.2025.117259_bb0195","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1097\/01.ju.0000141580.30910.57","article-title":"Cell lines used in prostate cancer research: a compendium of old and new lines--part 1","volume":"173","author":"Sobel","year":"2005","journal-title":"J. Urol."},{"key":"10.1016\/j.taap.2025.117259_bb0200","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1006\/exnr.2001.7680","article-title":"Involvement of oxidative stress in ascorbate-induced proapoptotic death of PC12 cells","volume":"169","author":"Song","year":"2001","journal-title":"Exp. Neurol."},{"key":"10.1016\/j.taap.2025.117259_bb0205","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1111\/cas.15728","article-title":"Development of drugs targeting hypoxia-inducible factor against tumor cells with VHL mutation: story of 127years","volume":"114","author":"Takamori","year":"2023","journal-title":"Cancer Sci."},{"key":"10.1016\/j.taap.2025.117259_bb0210","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1016\/j.bbalip.2018.06.015","article-title":"Expression of AGPAT2, an enzyme involved in the glycerophospholipid\/triacylglycerol biosynthesis pathway, is directly regulated by HIF-1 and promotes survival and etoposide resistance of cancer cells under hypoxia","volume":"1863","author":"Triantafyllou","year":"2018","journal-title":"Biochim. Biophys. Acta Mol. Cell Biol. Lipids"},{"key":"10.1016\/j.taap.2025.117259_bb0215","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1016\/0006-2952(90)90152-B","article-title":"Oxygen dependence of oxidative stress. Rate of NADPH supply for maintaining the GSH pool during hypoxia","volume":"39","author":"Tribble","year":"1990","journal-title":"Biochem. Pharmacol."},{"key":"10.1016\/j.taap.2025.117259_bb0220","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1038\/nprot.2006.179","article-title":"Sulforhodamine B colorimetric assay for cytotoxicity screening","volume":"1","author":"Vichai","year":"2006","journal-title":"Nat. Protoc."},{"key":"10.1016\/j.taap.2025.117259_bb0225","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1002\/iub.363","article-title":"Hypoxia regulates the ferrous iron uptake and reactive oxygen species level via divalent metal transporter 1 (DMT1) Exon1B by hypoxia-inducible factor-1","volume":"62","author":"Wang","year":"2010","journal-title":"IUBMB Life"},{"key":"10.1016\/j.taap.2025.117259_bb0230","doi-asserted-by":"crossref","DOI":"10.1172\/JCI159839","article-title":"Hypoxia-inducible factors: cancer progression and clinical translation","volume":"132","author":"Wicks","year":"2022","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.taap.2025.117259_bb0235","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/S0014-5793(02)03167-8","article-title":"The physiological role of dehydroascorbic acid","volume":"527","author":"Wilson","year":"2002","journal-title":"FEBS Lett."},{"key":"10.1016\/j.taap.2025.117259_bb0240","doi-asserted-by":"crossref","DOI":"10.1096\/fj.202300918R","article-title":"Newly uncovered biochemical and functional aspects of ferritin","volume":"37","author":"Yanatori","year":"2023","journal-title":"FASEB J."},{"key":"10.1016\/j.taap.2025.117259_bb0245","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/0006-2952(94)00544-V","article-title":"Involvement of NF-kappa B in the induction of NAD(P)H:quinone oxidoreductase (DT-diaphorase) by hypoxia, oltipraz and mitomycin C","volume":"49","author":"Yao","year":"1995","journal-title":"Biochem. Pharmacol."},{"key":"10.1016\/j.taap.2025.117259_bb0250","doi-asserted-by":"crossref","first-page":"10396","DOI":"10.1021\/ja4028346","article-title":"Ascorbic acid enhances Tet-mediated 5-methylcytosine oxidation and promotes DNA demethylation in mammals","volume":"135","author":"Yin","year":"2013","journal-title":"J. Am. Chem. Soc."}],"container-title":["Toxicology and Applied Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0041008X25000353?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0041008X25000353?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,3,10]],"date-time":"2025-03-10T05:25:30Z","timestamp":1741584330000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0041008X25000353"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4]]},"references-count":50,"alternative-id":["S0041008X25000353"],"URL":"https:\/\/doi.org\/10.1016\/j.taap.2025.117259","relation":{},"ISSN":["0041-008X"],"issn-type":[{"value":"0041-008X","type":"print"}],"subject":[],"published":{"date-parts":[[2025,4]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Effects of hypoxia and iron on ascorbic acid-mediated cytotoxicity in prostate cancer cell lines","name":"articletitle","label":"Article Title"},{"value":"Toxicology and Applied Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.taap.2025.117259","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Published by Elsevier Inc.","name":"copyright","label":"Copyright"}],"article-number":"117259"}}