{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T21:13:48Z","timestamp":1771017228463,"version":"3.50.1"},"reference-count":50,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,8,7]],"date-time":"2021-08-07T00:00:00Z","timestamp":1628294400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["PTDC\/MECONC\/29030\/2017"],"award-info":[{"award-number":["PTDC\/MECONC\/29030\/2017"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UID\/DTP\/0076\/POCI-01-0145-FEDER-006868"],"award-info":[{"award-number":["UID\/DTP\/0076\/POCI-01-0145-FEDER-006868"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["CEECINST\/00091\/2018"],"award-info":[{"award-number":["CEECINST\/00091\/2018"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011733","name":"Liga Portuguesa Contra o Cancro","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/501100011733","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomedicines"],"abstract":"<jats:p>Advanced prostate cancers frequently develop resistance to androgen-deprivation therapy with serious implications for patient survival. Considering their importance in this type of neoplasia, epigenetic modifications have drawn attention as alternative treatment strategies. The aim of this study was to assess the antitumoral effects of the combination of hydralazine, a DNA methylation inhibitor, with enzalutamide, an antagonist of the androgen receptor, in prostate cancer cell lines. Several biological parameters, such as cell viability, proliferation, DNA damage, and apoptosis, as well as clonogenic and invasive potential, were evaluated. The individual treatments with hydralazine and enzalutamide exerted growth-inhibitory effects in prostate cancer cells and their combined treatment displayed synergistic effects. The combination of these two drugs was very effective in decreasing malignant features of prostate cancer and may become an alternative therapeutic option for prostate cancer patient management.<\/jats:p>","DOI":"10.3390\/biomedicines9080976","type":"journal-article","created":{"date-parts":[[2021,8,8]],"date-time":"2021-08-08T21:49:41Z","timestamp":1628459381000},"page":"976","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Hydralazine and Enzalutamide: Synergistic Partners against Prostate Cancer"],"prefix":"10.3390","volume":"9","author":[{"given":"Nair","family":"Lopes","sequence":"first","affiliation":[{"name":"Cancer Biology and Epigenetics Group, Research Center of IPO Porto (CI-IPOP)\/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)\/Porto Comprehensive Cancer Center (Porto.CCC), Rua Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2151-7837","authenticated-orcid":false,"given":"Mariana Br\u00fctt","family":"Pacheco","sequence":"additional","affiliation":[{"name":"Cancer Biology and Epigenetics Group, Research Center of IPO Porto (CI-IPOP)\/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)\/Porto Comprehensive Cancer Center (Porto.CCC), Rua Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"}]},{"given":"Diana","family":"Soares-Fernandes","sequence":"additional","affiliation":[{"name":"Cancer Biology and Epigenetics Group, Research Center of IPO Porto (CI-IPOP)\/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)\/Porto Comprehensive Cancer Center (Porto.CCC), Rua Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4378-0820","authenticated-orcid":false,"given":"Margareta P.","family":"Correia","sequence":"additional","affiliation":[{"name":"Cancer Biology and Epigenetics Group, Research Center of IPO Porto (CI-IPOP)\/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)\/Porto Comprehensive Cancer Center (Porto.CCC), Rua Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"},{"name":"Department of Pathology and Molecular Immunology, School of Medicine and Biomedical Sciences, University of Porto (ICBAS-UP), Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal"}]},{"given":"V\u00e2nia","family":"Camilo","sequence":"additional","affiliation":[{"name":"Cancer Biology and Epigenetics Group, Research Center of IPO Porto (CI-IPOP)\/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)\/Porto Comprehensive Cancer Center (Porto.CCC), Rua Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3171-4666","authenticated-orcid":false,"given":"Rui","family":"Henrique","sequence":"additional","affiliation":[{"name":"Cancer Biology and Epigenetics Group, Research Center of IPO Porto (CI-IPOP)\/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)\/Porto Comprehensive Cancer Center (Porto.CCC), Rua Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"},{"name":"Department of Pathology and Molecular Immunology, School of Medicine and Biomedical Sciences, University of Porto (ICBAS-UP), Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal"},{"name":"Department of Pathology, Portuguese Oncology Institute of Porto (IPO Porto), Rua Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4186-5345","authenticated-orcid":false,"given":"Carmen","family":"Jer\u00f3nimo","sequence":"additional","affiliation":[{"name":"Cancer Biology and Epigenetics Group, Research Center of IPO Porto (CI-IPOP)\/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)\/Porto Comprehensive Cancer Center (Porto.CCC), Rua Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"},{"name":"Department of Pathology, Portuguese Oncology Institute of Porto (IPO Porto), Rua Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","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 Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1084\/jem.72.6.747","article-title":"Quantitative studies of prostatic secretion II. The effect of castration and of estrogen injection on the normal and on the hyperplastic prostate glands of dogs","volume":"72","author":"Huggins","year":"1940","journal-title":"J. Exp. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2905","DOI":"10.2217\/fon-2020-0557","article-title":"Apalutamide for the treatment of metastatic castration-sensitive prostate cancer","volume":"16","author":"Dror","year":"2020","journal-title":"Future Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1056\/NEJMoa1903307","article-title":"Apalutamide for Metastatic, Castration-Sensitive Prostate Cancer","volume":"381","author":"Chi","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1755","DOI":"10.1056\/NEJMoa1405095","article-title":"Enzalutamide in metastatic prostate cancer before chemotherapy","volume":"371","author":"Beer","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2197","DOI":"10.1056\/NEJMoa2003892","article-title":"Enzalutamide and Survival in Nonmetastatic, Castration-Resistant Prostate Cancer","volume":"382","author":"Sternberg","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1126\/science.1168175","article-title":"Development of a second-generation antiandrogen for treatment of advanced prostate cancer","volume":"324","author":"Tran","year":"2009","journal-title":"Science"},{"key":"ref_8","first-page":"365","article-title":"Mechanisms of resistance in castration-resistant prostate cancer (CRPC)","volume":"4","author":"Chandrasekar","year":"2015","journal-title":"Transl. Androl. Urol."},{"key":"ref_9","first-page":"101","article-title":"Targeting treatment options for castration-resistant prostate cancer","volume":"9","author":"Miller","year":"2021","journal-title":"Am. J. Clin. Exp. Urol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1002\/cncr.23304","article-title":"Efficacy of androgen deprivation therapy (ADT) in patients with advanced prostate cancer: Association between Gleason score, prostate-specific antigen level, and prior ADT exposure with duration of ADT effect","volume":"112","author":"Ross","year":"2008","journal-title":"Cancer"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.eururo.2021.03.005","article-title":"Recent Advances in Epigenetic Biomarkers and Epigenetic Targeting in Prostate Cancer","volume":"80","author":"Kumaraswamy","year":"2021","journal-title":"Eur. Urol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1016\/j.eururo.2011.06.035","article-title":"Epigenetics in prostate cancer: Biologic and clinical relevance","volume":"60","author":"Bastian","year":"2011","journal-title":"Eur. Urol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/S0002-9149(02)03336-2","article-title":"Pharmacologic therapy for patients with chronic heart failure and reduced systolic function: Review of trials and practical considerations","volume":"91","author":"Klein","year":"2003","journal-title":"Am. J. Cardiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1136\/bmj.327.7421.955","article-title":"Hydralazine for treatment of severe hypertension in pregnancy: Meta-analysis","volume":"327","author":"Magee","year":"2003","journal-title":"BMJ"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2197","DOI":"10.4049\/jimmunol.140.7.2197","article-title":"Hydralazine and procainamide inhibit T cell DNA methylation and induce autoreactivity","volume":"140","author":"Cornacchia","year":"1988","journal-title":"J. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1002\/cmdc.200900017","article-title":"Molecular modeling and molecular dynamics studies of hydralazine with human DNA methyltransferase 1","volume":"4","author":"Singh","year":"2009","journal-title":"ChemMedChem"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.ctrv.2017.01.004","article-title":"Clinical and biological effects of demethylating agents on solid tumours\u2014A systematic review","volume":"54","author":"Linnekamp","year":"2017","journal-title":"Cancer Treat. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"5950","DOI":"10.18632\/oncotarget.1909","article-title":"Anti-neoplastic properties of hydralazine in prostate cancer","volume":"5","author":"Sousa","year":"2014","journal-title":"Oncotarget"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1038\/s41419-020-03279-y","article-title":"JmjC-KDMs KDM3A and KDM6B modulate radioresistance under hypoxic conditions in esophageal squamous cell carcinoma","volume":"11","author":"Lameirinhas","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1002\/cam4.981","article-title":"Impact of treatment on progression to castration-resistance, metastases, and death in men with localized high-grade prostate cancer","volume":"6","author":"Miller","year":"2017","journal-title":"Cancer Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1517\/17425255.2014.947263","article-title":"Hydralazine-valproate: A repositioned drug combination for the epigenetic therapy of cancer","volume":"10","author":"Coronel","year":"2014","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.tranon.2014.03.001","article-title":"A Phase I Protocol of Hydralazine and Valproic Acid in Advanced, Previously Treated Solid Cancers","volume":"7","author":"Bauman","year":"2014","journal-title":"Transl. Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"20271","DOI":"10.1038\/s41598-019-56854-5","article-title":"Reversal of increased mammary tumorigenesis by valproic acid and hydralazine in offspring of dams fed high fat diet during pregnancy","volume":"9","author":"Andrade","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_24","first-page":"1570","article-title":"Inhibition of telomerase potentiates enzalutamide efficiency of androgen-sensitive human prostate cancer cells","volume":"22","author":"Gecgel","year":"2017","journal-title":"J. Buon."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.bbrc.2016.11.021","article-title":"Additive inhibitory effects of simvastatin and enzalutamide on androgen-sensitive LNCaP and VCaP prostate cancer cells","volume":"481","author":"Pennanen","year":"2016","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1158\/1535-7163.MCT-20-0228","article-title":"Antitumor Activity of NLG207 (Formerly CRLX101) in Combination with Enzalutamide in Preclinical Prostate Cancer Models","volume":"20","author":"Schmidt","year":"2021","journal-title":"Mol. Cancer Ther."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1158\/1078-0432.CCR-18-1589","article-title":"Epigenetic Therapy with Panobinostat Combined with Bicalutamide Rechallenge in Castration-Resistant Prostate Cancer","volume":"25","author":"Ferrari","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"ref_28","first-page":"1321","article-title":"Gefitinib and bicalutamide show synergistic effects in primary cultures of prostate cancer derived from androgen-dependent naive patients","volume":"18","author":"Festuccia","year":"2007","journal-title":"Oncol. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1186\/s13046-015-0168-z","article-title":"Combination of curcumin and bicalutamide enhanced the growth inhibition of androgen-independent prostate cancer cells through SAPK\/JNK and MEK\/ERK1\/2-mediated targeting NF-\u03baB\/p65 and MUC1-C","volume":"34","author":"Li","year":"2015","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"425","DOI":"10.3892\/ijo.2012.1487","article-title":"Synergistic activity of the mTOR inhibitor ridaforolimus and the antiandrogen bicalutamide in prostate cancer models","volume":"41","author":"Squillace","year":"2012","journal-title":"Int. J. Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2935","DOI":"10.1038\/s41467-020-16735-2","article-title":"A cancer drug atlas enables synergistic targeting of independent drug vulnerabilities","volume":"11","author":"Narayan","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.canlet.2016.10.036","article-title":"Combination of sorafenib and enzalutamide as a potential new approach for the treatment of castration-resistant prostate cancer","volume":"385","author":"Wu","year":"2017","journal-title":"Cancer Lett."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1016\/j.yexmp.2011.09.007","article-title":"Combination of thiazolidinedione and hydralazine suppresses proliferation and induces apoptosis by PPAR\u03b3 up-expression in MDA-MB-231 cells","volume":"91","author":"Jiang","year":"2011","journal-title":"Exp. Mol. Pathol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"21875","DOI":"10.18632\/oncotarget.7871","article-title":"The antihypertensive drug hydralazine activates the intrinsic pathway of apoptosis and causes DNA damage in leukemic T cells","volume":"7","author":"Lucendo","year":"2016","journal-title":"Oncotarget"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e22338","DOI":"10.1002\/jbt.22338","article-title":"Synergistic effects of hormone therapy drugs and usnic acid on hormone receptor-positive breast and prostate cancer cells","volume":"33","author":"Eryilmaz","year":"2019","journal-title":"J. Biochem. Mol. Toxicol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1833","DOI":"10.1158\/1535-7163.MCT-17-1023","article-title":"AKR1C3 Inhibitor KV-37 Exhibits Antineoplastic Effects and Potentiates Enzalutamide in Combination Therapy in Prostate Adenocarcinoma Cells","volume":"17","author":"Verma","year":"2018","journal-title":"Mol. Cancer Ther."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2791","DOI":"10.1158\/1535-7163.MCT-15-0861","article-title":"Wedelolactone, an Anti-inflammatory Botanical, Interrupts c-Myc Oncogenic Signaling and Synergizes with Enzalutamide to Induce Apoptosis in Prostate Cancer Cells","volume":"15","author":"Sarveswaran","year":"2016","journal-title":"Mol. Cancer Ther."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"9086","DOI":"10.18632\/oncotarget.3602","article-title":"Inhibition of the HER2-YB1-AR axis with Lapatinib synergistically enhances Enzalutamide anti-tumor efficacy in castration resistant prostate cancer","volume":"6","author":"Shiota","year":"2015","journal-title":"Oncotarget"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1002\/pros.22813","article-title":"Inhibition of RSK\/YB-1 signaling enhances the anti-cancer effect of enzalutamide in prostate cancer","volume":"74","author":"Shiota","year":"2014","journal-title":"Prostate"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e12370","DOI":"10.1111\/cpr.12370","article-title":"Proliferation inhibition of cisplatin-resistant ovarian cancer cells using drugs screened by integrating a metabolic model and transcriptomic data","volume":"50","author":"Motamedian","year":"2017","journal-title":"Cell Prolif."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1007\/s00280-008-0773-z","article-title":"Hydralazine inhibits human cervical cancer cell growth in vitro in association with APC demethylation and re-expression","volume":"63","author":"Song","year":"2009","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/1743-422X-4-18","article-title":"The effects of DNA methylation and histone deacetylase inhibitors on human papillomavirus early gene expression in cervical cancer, an in vitro and clinical study","volume":"4","author":"Mohar","year":"2007","journal-title":"Virol. J."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1158\/1535-7163.MCT-19-0378","article-title":"Antitumor Activity of the IGF-1\/IGF-2-Neutralizing Antibody Xentuzumab (BI 836845) in Combination with Enzalutamide in Prostate Cancer Models","volume":"19","author":"Hofmann","year":"2020","journal-title":"Mol. Cancer Ther."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1038\/s41391-017-0023-8","article-title":"The molecular biology of prostate cancer: Current understanding and clinical implications","volume":"21","author":"Gandhi","year":"2018","journal-title":"Prostate Cancer Prostatic Dis."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.ejphar.2016.03.021","article-title":"In vitro and in vivo study of hydralazine, a potential anti-angiogenic agent","volume":"779","author":"Zhang","year":"2016","journal-title":"Eur. J. Pharmacol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1124\/jpet.119.261040","article-title":"A Novel Small Molecule Inhibits Tumor Growth and Synergizes Effects of Enzalutamide on Prostate Cancer","volume":"371","author":"Cheng","year":"2019","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.canlet.2017.08.014","article-title":"Androgen-deprivation therapy with enzalutamide enhances prostate cancer metastasis via decreasing the EPHB6 suppressor expression","volume":"408","author":"Chen","year":"2017","journal-title":"Cancer Lett."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Candelaria, M., de la Cruz-Hernandez, E., Taja-Chayeb, L., Perez-Cardenas, E., Trejo-Becerril, C., Gonzalez-Fierro, A., Chavez-Blanco, A., Soto-Reyes, E., Dominguez, G., and Trujillo, J.E. (2012). DNA methylation-independent reversion of gemcitabine resistance by hydralazine in cervical cancer cells. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0029181"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.clml.2012.01.005","article-title":"Epigenetic therapy with hydralazine and magnesium valproate reverses imatinib resistance in patients with chronic myeloid leukemia","volume":"12","author":"Cervera","year":"2012","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"ref_50","first-page":"140","article-title":"Radiosensitization of cervical cancer cells with epigenetic drugs hydralazine and valproate","volume":"35","author":"Mani","year":"2014","journal-title":"Eur. J. Gynaecol. Oncol."}],"container-title":["Biomedicines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2227-9059\/9\/8\/976\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:42:20Z","timestamp":1760164940000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2227-9059\/9\/8\/976"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,7]]},"references-count":50,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["biomedicines9080976"],"URL":"https:\/\/doi.org\/10.3390\/biomedicines9080976","relation":{},"ISSN":["2227-9059"],"issn-type":[{"value":"2227-9059","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,7]]}}}