{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:36:08Z","timestamp":1785429368269,"version":"3.56.0"},"reference-count":69,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T00:00:00Z","timestamp":1783728000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science, Technology, and Innovation of Colombia","award":["856 of 2017"],"award-info":[{"award-number":["856 of 2017"]}]},{"name":"Universidad del Sin\u00fa"},{"id":[{"id":"https:\/\/ror.org\/013ys5k90","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Dimethyl fumarate (DMF) is a clinically approved fumarate ester with pleiotropic effects and a promising candidate for drug repurposing in cancer. Here, we investigated whether low-dose DMF could modulate docetaxel (DCT) responses in prostate cancer cells. PC-3, LNCaP, and RWPE-1 cells were exposed to DMF and DCT individually or in combination, and cell viability, drug interaction profiles, apoptosis, oxidative stress, mitochondrial mass, glutathione status, glucose consumption, lactate production, LDHA\/SOD2 expression, and oxygen consumption were evaluated. Low-dose DMF and DCT were well-tolerated in RWPE-1 normal prostate cells. In prostate cancer cells, the DMF\u2013DCT combination was cytotoxic and strongly dose- and ratio-dependent, with the most favorable responses at higher exposures and under balanced or DCT-enriched regimens. DMF-DCT-treated LNCaP cells showed reduced viability, decreased lactate production, increased glucose consumption, mitochondrial dysfunction, oxidative stress, downregulation of LDHA and SOD2, and caspase-associated apoptosis. In contrast, PC-3 cells showed greater combinatorial susceptibility, a docetaxel dose-sparing effect, and a low glycolytic profile, with concomitant cytotoxicity and mitochondrial dysfunction. These findings identify DMF as a context-dependent metabolic modulator of docetaxel response, supporting further evaluation of DMF\u2013DCT combinations as a potential therapeutic strategy in prostate cancer.<\/jats:p>","DOI":"10.3390\/ijms27146209","type":"journal-article","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T08:53:58Z","timestamp":1783932838000},"page":"6209","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Metabolic Modulation by Dimethyl Fumarate Alters Docetaxel Responses in Prostate Cancer Cells"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6952-7570","authenticated-orcid":false,"given":"Andr\u00e9s","family":"Coneo-Pretelt","sequence":"first","affiliation":[{"name":"Grupo de Investigaci\u00f3n Biom\u00e9dica y Biolog\u00eda Molecular, Facultad de Ciencias de la Salud, Universidad del Sin\u00fa, Monter\u00eda 230001, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8698-612X","authenticated-orcid":false,"given":"Ana","family":"Pe\u00f1ata-Taborda","sequence":"additional","affiliation":[{"name":"Grupo de Investigaci\u00f3n Biom\u00e9dica y Biolog\u00eda Molecular, Facultad de Ciencias de la Salud, Universidad del Sin\u00fa, Monter\u00eda 230001, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3332-7814","authenticated-orcid":false,"given":"Lyda","family":"Espitia-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Grupo de Investigaci\u00f3n Biom\u00e9dica y Biolog\u00eda Molecular, Facultad de Ciencias de la Salud, Universidad del Sin\u00fa, Monter\u00eda 230001, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa","family":"Jim\u00e9nez-Vidal","sequence":"additional","affiliation":[{"name":"Grupo de Investigaci\u00f3n Biom\u00e9dica y Biolog\u00eda Molecular, Facultad de Ciencias de la Salud, Universidad del Sin\u00fa, Monter\u00eda 230001, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2370-1841","authenticated-orcid":false,"given":"Mario","family":"Negrette-Guzm\u00e1n","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias B\u00e1sicas, Escuela de Medicina, Universidad Industrial de Santander, Bucaramanga 680002, Colombia"},{"name":"Grupo de Investigaci\u00f3n en Farmacolog\u00eda y Metabolismo (FARMET), Universidad Industrial de Santander, Bucaramanga 680001, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8338-5174","authenticated-orcid":false,"given":"Nathalia","family":"Jones-Cifuentes","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias B\u00e1sicas, Escuela de Medicina, Universidad Industrial de Santander, Bucaramanga 680002, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5323-0422","authenticated-orcid":false,"given":"Bladimiro","family":"Rinc\u00f3n-Orozco","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias B\u00e1sicas, Escuela de Medicina, Universidad Industrial de Santander, Bucaramanga 680002, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Aristiz\u00e1bal-Guti\u00e9rrez","sequence":"additional","affiliation":[{"name":"Departamento de Farmacia, Facultad de Ciencias, Universidad Nacional de Colombia, Bogot\u00e1 111321, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2487-9967","authenticated-orcid":false,"given":"Pedro","family":"Espitia-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Grupo de Investigaci\u00f3n Biom\u00e9dica y Biolog\u00eda Molecular, Facultad de Ciencias de la Salud, Universidad del Sin\u00fa, Monter\u00eda 230001, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,11]]},"reference":[{"key":"ref_1","first-page":"209","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA A Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Ranasinghe, W.K.B., Xiao, L., Kovac, S., Chang, M., Michiels, C., Bolton, D., Shulkes, A., Baldwin, G.S., and Patel, O. (2013). The Role of Hypoxia-Inducible Factor 1\u03b1 in Determining the Properties of Castrate-Resistant Prostate Cancers. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0054251"},{"key":"ref_3","first-page":"1365","article-title":"Increasing prevalence of metastatic castration-resistant prostate cancer in a managed care population in the United States","volume":"32","author":"Wallace","year":"2021","journal-title":"Cancer Causes Control."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"334","DOI":"10.4103\/1008-682X.122593","article-title":"Chemotherapy and its evolving role in the management of advanced prostate cancer","volume":"16","author":"Schweizer","year":"2014","journal-title":"Asian J. Androl."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"E637","DOI":"10.5489\/cuaj.7173","article-title":"Incidence and mortality trends of metastatic prostate cancer: Surveillance, Epidemiology, and End Results database analysis","volume":"15","author":"Zhang","year":"2021","journal-title":"Can. Urol. Assoc. J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e222246","DOI":"10.1001\/jamanetworkopen.2022.2246","article-title":"Trends in Incidence of Metastatic Prostate Cancer in the US","volume":"5","author":"Desai","year":"2022","journal-title":"JAMA Netw. Open"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"188481","DOI":"10.1016\/j.bbcan.2020.188481","article-title":"Mechanisms of docetaxel resistance in prostate cancer: The key role played by miRNAs","volume":"1875","author":"Rizzo","year":"2021","journal-title":"Biochim. Et. Biophys. Acta (BBA) -Rev. Cancer"},{"key":"ref_8","unstructured":"Observatorio Nacional de Salud (2015). Quinto Informe ONS: Carga de Enfermedad por Enfermedades Cr\u00f3nicas no Transmisibles y Discapacidad en Colombia."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.toxlet.2010.08.009","article-title":"Protective effect of sulforaphane against cisplatin-induced mitochondrial alterations and impairment in the activity of NAD(P)H: Quinone oxidoreductase 1 and \u03b3 glutamyl cysteine ligase: Studies in mitochondria isolated from rat kidney and in LLC-PK1 cells","volume":"199","author":"Tapia","year":"2010","journal-title":"Toxicol. Lett."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Barrera, G., Cucci, M.A., Grattarola, M., Dianzani, C., Muzio, G., and Pizzimenti, S. (2021). Control of oxidative stress in cancer chemoresistance: Spotlight on Nrf2 role. Antioxidants, 10.","DOI":"10.3390\/antiox10040510"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e202100641","DOI":"10.1002\/cbic.202100641","article-title":"Oxidative Stress in Cancer Therapy: Friend or Enemy?","volume":"23","author":"Azmanova","year":"2022","journal-title":"ChemBioChem"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"172513","DOI":"10.1016\/j.ejphar.2019.172513","article-title":"Combinations of the antioxidants sulforaphane or curcumin and the conventional antineoplastics cisplatin or doxorubicin as prospects for anticancer chemotherapy","volume":"859","year":"2019","journal-title":"Eur. J. Pharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1126\/science.aan4665","article-title":"Dimethyl fumarate targets GAPDH and aerobic glycolysis to modulate immunity","volume":"360","author":"Kornberg","year":"2018","journal-title":"Science"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1158\/1535-7163.MCT-16-0405","article-title":"Dimethyl Fumarate Controls the NRF2\/DJ-1 Axis in Cancer Cells: Therapeutic Applications","volume":"16","author":"Saidu","year":"2017","journal-title":"Mol. Cancer Ther."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1746","DOI":"10.4049\/jimmunol.1900740","article-title":"Fumarate Upregulates Surface Expression of ULBP2\/ULBP5 by Scavenging Glutathione Antioxidant Capacity","volume":"204","author":"Droujinine","year":"2020","journal-title":"J. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Brennan, M.S., Matos, M.F., Li, B., Hronowski, X., Gao, B., Juhasz, P., Rhodes, K.J., and Scannevin, R.H. (2015). Dimethyl fumarate and monoethyl fumarate exhibit differential effects on KEAP1, NRF2 activation, and glutathione depletion in vitro. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0120254"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2864","DOI":"10.1093\/hmg\/ddx167","article-title":"Dimethyl fumarate mediates Nrf2-dependent mitochondrial biogenesis in mice and humans","volume":"26","author":"Hayashi","year":"2017","journal-title":"Hum. Mol. Genet"},{"key":"ref_18","first-page":"597","article-title":"Structural Study of Monomethyl Fumarate-Bound Human GAPDH","volume":"42","author":"Park","year":"2019","journal-title":"Mol. Cells"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"115153","DOI":"10.1016\/j.bcp.2022.115153","article-title":"Taming metabolic competition via glycolysis inhibition for safe and potent tumor immunotherapy","volume":"202","author":"Lei","year":"2022","journal-title":"Biochem Pharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Chen, K., Wu, S., Ye, S., Huang, H., Zhou, Y., Zhou, H., Wu, S., Mao, Y., Shangguan, F., and Lan, L. (2021). Dimethyl Fumarate Induces Metabolic Crisie to Suppress Pancreatic Carcinoma. Front Pharmacol., 12.","DOI":"10.3389\/fphar.2021.617714"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e562","DOI":"10.1212\/NXI.0000000000000562","article-title":"Breaking the cycle: Reversal of flux in the tricarboxylic acid cycle by dimethyl fumarate","volume":"6","author":"Gafson","year":"2019","journal-title":"Neurol. Neuroimmunol. Neuroinflammation"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3929","DOI":"10.1111\/bph.13184","article-title":"Dimethyl fumarate induces necroptosis in colon cancer cells through GSH depletion\/ROS increase\/MAPKs activation pathway","volume":"172","author":"Xie","year":"2015","journal-title":"Br. J. Pharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"9088","DOI":"10.18632\/oncotarget.24144","article-title":"Dimethyl fumarate is highly cytotoxic in KRAS mutated cancer cells but spares non-tumorigenic cells","volume":"9","author":"Bretagne","year":"2018","journal-title":"Oncotarget"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Cubides-Cely, S., David Castro, A., Prado-Guevara, P., Mantilla-Hern\u00e1ndez, J.C., and Negrette-Guzm\u00e1n, M. (2025). An Experimental Rat Model for Simultaneous Induction of Peripheral Neuropathy and Myelotoxicity by Docetaxel Administration: Evaluating the Protective Role of Dimethyl Fumarate. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26125859"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Zhang, M., Jing, Y., and Cui, Q. (2025). Repurposing dimethyl fumarate for cancer therapy: Current evidence and future directions. Front Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1721876"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.fct.2016.12.020","article-title":"Sulforaphane induces differential modulation of mitochondrial biogenesis and dynamics in normal cells and tumor cells","volume":"100","author":"Vega","year":"2017","journal-title":"Food Chem. Toxicol. Int. J. Publ. Br. Ind. Biol. Res. Assoc."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"9.19.1","DOI":"10.1002\/0471141755.ph0919s72","article-title":"Drug Combinations: Tests and Analysis with Isoboles","volume":"72","author":"Tallarida","year":"2016","journal-title":"Curr. Protoc. Pharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1124\/jpet.112.193474","article-title":"Revisiting the Isobole and Related Quantitative Methods for Assessing Drug Synergism","volume":"342","author":"Tallarida","year":"2012","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e32213","DOI":"10.7554\/eLife.32213","article-title":"Selective eradication of cancer displaying hyperactive Akt by exploiting the metabolic consequences of Akt activation","volume":"7","author":"Nogueira","year":"2018","journal-title":"eLife"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Pe\u00f1ata-Taborda, A., Espitia-P\u00e9rez, P., Espitia-P\u00e9rez, L., Coneo-Pretelt, A., Brango, H., Ricardo-Caldera, D., Arteaga-Arroyo, G., Jim\u00e9nez-Vidal, L., Galeano-P\u00e1ez, C., and Pastor-Sierra, K. (2025). Combination of Low-Dose Sulforaphane and Docetaxel on Mitochondrial Function and Metabolic Reprogramming in Prostate Cancer Cell Lines. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26031013"},{"key":"ref_31","first-page":"255","article-title":"DMF induces apoptosis in human androgen-independent prostate cancer PC3 cells in vitro","volume":"36","author":"Fang","year":"2007","journal-title":"Zhejiang Da Xue Xue Bao Yi Xue Ban"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1007\/s11626-016-0069-2","article-title":"Dimethylfumarate induces cell cycle arrest and apoptosis via regulating intracellular redox systems in HeLa cells","volume":"52","author":"Han","year":"2016","journal-title":"Vitr. Cell Dev. Biol. Anim."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"104500","DOI":"10.1016\/j.msard.2023.104500","article-title":"Comparative pharmacokinetics and bioavailability of monomethyl fumarate following a single oral dose of Bafiertam\u00ae (monomethyl fumarate) versus Vumerity\u00ae (diroximel fumarate)","volume":"70","author":"Rousseau","year":"2023","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Kopincova, J., and Bernatova, I. (2025). Dimethyl Fumarate vs. Monomethyl Fumarate: Unresolved Pharmacologic Issues. Pharmaceutics, 17.","DOI":"10.3390\/pharmaceutics17121506"},{"key":"ref_35","first-page":"21","article-title":"Pharmacokinetics and Toxicities of Oral Docetaxel Formulations Co-Administered with Ritonavir in Phase I Trials","volume":"13","author":"Vermunt","year":"2021","journal-title":"Clin. Pharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"rs10","DOI":"10.1126\/scisignal.aaf7694","article-title":"Chemical proteomic map of dimethyl fumarate-sensitive cysteines in primary human T cells","volume":"9","author":"Blewett","year":"2016","journal-title":"Sci. Signal"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"997","DOI":"10.3892\/etm.2021.10429","article-title":"ChaC glutathione specific \u03b3-glutamylcyclotransferase 1 inhibits cell viability and increases the sensitivity of prostate cancer cells to docetaxel by inducing endoplasmic reticulum stress and ferroptosis","volume":"22","author":"He","year":"2021","journal-title":"Exp. Ther. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1093\/jb\/mvab025","article-title":"Targeting Nrf2-antioxidant signalling reverses acquired cabazitaxel resistance in prostate cancer cells","volume":"170","author":"Endo","year":"2021","journal-title":"J. Biochem"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1442","DOI":"10.1096\/fj.11-199869","article-title":"Glutathione-dependent reductive stress triggers mitochondrial oxidation and cytotoxicity","volume":"26","author":"Zhang","year":"2012","journal-title":"Faseb J."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"6093903","DOI":"10.1155\/2017\/6093903","article-title":"Dimethyl Fumarate Induces Glutathione Recycling by Upregulation of Glutathione Reductase","volume":"2017","author":"Hoffmann","year":"2017","journal-title":"Oxidative Med. Cell Longev."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"5136957","DOI":"10.1155\/2020\/5136957","article-title":"Reductive Stress-Induced Mitochondrial Dysfunction and Cardiomyopathy","volume":"2020","author":"Ma","year":"2020","journal-title":"Oxidative Med. Cell Longev."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"101050","DOI":"10.1016\/j.redox.2018.11.008","article-title":"Electrophiles modulate glutathione reductase activity via alkylation and upregulation of glutathione biosynthesis","volume":"21","author":"Jobbagy","year":"2019","journal-title":"Redox Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1111\/j.1582-4934.2009.00697.x","article-title":"The mitochondrial death pathway: A promising therapeutic target in diseases","volume":"13","author":"Gupta","year":"2009","journal-title":"J. Cell. Mol. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"11","DOI":"10.5483\/BMBRep.2008.41.1.011","article-title":"The role of mitochondria in apoptosis","volume":"41","author":"Jeong","year":"2008","journal-title":"BMB Rep."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"13627","DOI":"10.1007\/s13277-016-5285-6","article-title":"Dimethylfumarate inhibits melanoma cell proliferation via p21 and p53 induction and bcl-2 and cyclin B1 downregulation","volume":"37","author":"Kaluzki","year":"2016","journal-title":"Tumor Biol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Kaluzki, I., Hailemariam-Jahn, T., Doll, M., Kaufmann, R., Balermpas, P., Z\u00f6ller, N., Kippenberger, S., and Meissner, M. (2019). Dimethylfumarate Inhibits Colorectal Carcinoma Cell Proliferation: Evidence for Cell Cycle Arrest, Apoptosis and Autophagy. Cells, 8.","DOI":"10.3390\/cells8111329"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.semcdb.2014.07.002","article-title":"Therapeutic exploitation of necroptosis for cancer therapy","volume":"35","author":"Fulda","year":"2014","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Deretic, V. (2008). LC3 and Autophagy. Autophagosome and Phagosome, Humana Press.","DOI":"10.1007\/978-1-59745-157-4"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1038\/nrm2970","article-title":"Molecular mechanisms of necroptosis: An ordered cellular explosion","volume":"11","author":"Vandenabeele","year":"2010","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Dueregger, A., Sch\u00f6pf, B., Eder, T., H\u00f6fer, J., Gnaiger, E., Aufinger, A., Kenner, L., Perktold, B., Ramoner, R., and Klocker, H. (2015). Differential Utilization of Dietary Fatty Acids in Benign and Malignant Cells of the Prostate. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0135704"},{"key":"ref_51","first-page":"4367","article-title":"Mitochondrial oncobioenergetics of prostate tumorigenesis","volume":"18","author":"Vayalil","year":"2019","journal-title":"Oncol. Lett."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1042\/CS20140101","article-title":"The Bioenergetic Health Index: A new concept in mitochondrial translational research","volume":"127","author":"Chacko","year":"2014","journal-title":"Clin. Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"4579","DOI":"10.4161\/cc.22852","article-title":"p53 expression controls prostate cancer sensitivity to chemotherapy and the MDM2 inhibitor Nutlin-3","volume":"11","author":"Chappell","year":"2012","journal-title":"Cell Cycle"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2175","DOI":"10.1080\/15384101.2018.1520565","article-title":"P53 enhances apoptosis induced by doxorubicin only under conditions of severe DNA damage","volume":"17","author":"Lin","year":"2018","journal-title":"Cell Cycle"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1158\/1541-7786.MCR-10-0235","article-title":"Loss of PTEN permits CXCR4-mediated tumorigenesis through ERK1\/2 in prostate cancer cells","volume":"9","author":"Chetram","year":"2011","journal-title":"Mol. Cancer Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1038\/nrurol.2018.9","article-title":"Clinical implications of PTEN loss in prostate cancer","volume":"15","author":"Jamaspishvili","year":"2018","journal-title":"Nat. Rev. Urol."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Pfragner, R., and Freshney, R.I. (2005). Culture of Human Tumor Cells, John Wiley & Sons.","DOI":"10.1002\/0471747599.cac024"},{"key":"ref_58","unstructured":"Freshney, R.I. (2015). Culture of Animal Cells: A Manual of Basic Technique and Specialized Applications, John Wiley & Sons."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1038\/bjc.2014.166","article-title":"Guidelines for the use of cell lines in biomedical research","volume":"111","author":"Geraghty","year":"2014","journal-title":"Br. J. Cancer"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1080\/21655979.2019.1657327","article-title":"Epigallocatechin gallate (EGCG) suppresses growth and tumorigenicity in breast cancer cells by downregulation of miR-25","volume":"10","author":"Zan","year":"2019","journal-title":"Bioengineered"},{"key":"ref_61","unstructured":"(2009). Biological Evaluation of Medical Devices Part 5: Tests for in Vitro Cytotoxicity 2009-06 (Standard No. ISO 10993-5:2009)."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"pdb.prot087379","DOI":"10.1101\/pdb.prot087379","article-title":"Crystal Violet Assay for Determining Viability of Cultured Cells","volume":"2016","author":"Feoktistova","year":"2016","journal-title":"Cold Spring Harb. Protoc."},{"key":"ref_63","first-page":"3065","article-title":"Establishment and characterization of the gemcitabine-resistant human pancreatic cancer cell line SW1990\/gemcitabine","volume":"18","author":"Yu","year":"2019","journal-title":"Oncol. Lett."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Wu, D., and Yotnda, P. (2011). Production and detection of reactive oxygen species (ROS) in cancers. J. Vis. Exp., 3357.","DOI":"10.3791\/3357"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1656","DOI":"10.1016\/j.freeradbiomed.2011.07.015","article-title":"Role of oxidative stress in lysosomal membrane permeabilization and apoptosis induced by gentamicin, an aminoglycoside antibiotic","volume":"51","author":"Denamur","year":"2011","journal-title":"Free Radic. Biol. Med."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Cui, J., Qu, Z., Harata-Lee, Y., Nwe Aung, T., Shen, H., Wang, W., and Adelson, D.L. (2019). Cell cycle, energy metabolism and DNA repair pathways in cancer cells are suppressed by Compound Kushen Injection. BMC Cancer, 19.","DOI":"10.1186\/s12885-018-5230-8"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Valvona, C.J., and Fillmore, H.L. (2018). Oxamate, but Not Selective Targeting of LDH-A, Inhibits Medulloblastoma Cell Glycolysis, Growth and Motility. Brain Sci., 8.","DOI":"10.3390\/brainsci8040056"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Yadav, S., Bhagat, S.D., Gupta, A., Samaiya, A., Srivastava, A., and Shukla, S.J.B.C. (2019). Dietary-phytochemical mediated reversion of cancer-specific splicing inhibits Warburg effect in head and neck cancer. BMC Cancer, 19.","DOI":"10.1186\/s12885-019-6257-1"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1530\/JME-13-0090","article-title":"Hypoxia upregulates the gene expression of mitochondrial aconitase in prostate carcinoma cells","volume":"51","author":"Tsui","year":"2013","journal-title":"J. Mol. Endocrinol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/14\/6209\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T08:57:00Z","timestamp":1783933020000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/14\/6209"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,11]]},"references-count":69,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["ijms27146209"],"URL":"https:\/\/doi.org\/10.3390\/ijms27146209","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,11]]}}}