{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T05:59:38Z","timestamp":1772690378733,"version":"3.50.1"},"reference-count":64,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,9,23]],"date-time":"2022-09-23T00:00:00Z","timestamp":1663891200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FEDER\u2014Fundo Europeu de Desenvolvimento Regional","award":["IF\/00092\/2014\/CP1255\/CT0004"],"award-info":[{"award-number":["IF\/00092\/2014\/CP1255\/CT0004"]}]},{"name":"FCT and FEDER (European Union)","award":["IF\/00092\/2014\/CP1255\/CT0004"],"award-info":[{"award-number":["IF\/00092\/2014\/CP1255\/CT0004"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Drug repurposing is a strategy that can speed up and find novel clinical uses for already-approved drugs for several diseases, such as cancer. This process is accelerated compared to the development of new drugs because these compounds have already been tested in clinical trials and data related to their pharmacokinetics is already described, reducing the costs and time associated with the development of new anticancer therapeutics. Several studies suggest that the repurposing of fluphenazine for cancer therapy may be a promising approach, as this drug proved to reduce the viability of diverse cancer cell lines. In this review, intensive research of the literature was performed related to the anticancer potential of fluphenazine in different human cancer cells. We have found several research articles on the cytotoxic effect of fluphenazine in lung, breast, colon, liver, brain, leukemia, oral, ovarian, and skin cancer and have summarized the main findings in this review. Taken together, these findings suggest that fluphenazine may regulate the cell cycle, reduce cell proliferation, and cause apoptosis in several types of cancer cells, besides being an established calmodulin inhibitor. It was also found that this drug is able to target cancer-related proteins, such as ABCB1 and P-glycoprotein as well as to regulate the Akt and Wnt signaling pathways. Some studies also refer this drug causes DNA alterations and interferes with cell invasion and migration ability as well as with ROS generation. Collectively, these results imply that fluphenazine may be a favorable compound for further research in oncologic therapy.<\/jats:p>","DOI":"10.3390\/biom12101360","type":"journal-article","created":{"date-parts":[[2022,9,25]],"date-time":"2022-09-25T21:14:28Z","timestamp":1664140468000},"page":"1360","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Antipsychotic Drug Fluphenazine against Human Cancer Cells"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1420-5042","authenticated-orcid":false,"given":"Diana","family":"Duarte","sequence":"first","affiliation":[{"name":"OncoPharma Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Doutor Pl\u00e1cido da Costa, s\/n, 4200-450 Porto, Portugal"},{"name":"Faculty of Pharmacy, University of Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal"},{"name":"CINTESIS@RISE, Faculty of Medicine, University of Porto, Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1283-1042","authenticated-orcid":false,"given":"Nuno","family":"Vale","sequence":"additional","affiliation":[{"name":"OncoPharma Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Doutor Pl\u00e1cido da Costa, s\/n, 4200-450 Porto, Portugal"},{"name":"CINTESIS@RISE, Faculty of Medicine, University of Porto, Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"},{"name":"Department of Community Medicine, Health Information and Decision (MEDCIDS), Faculty of Medicine, University of Porto, Rua Doutor Pl\u00e1cido da Costa, s\/n, 4200-450 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21708","article-title":"Cancer Statistics, 2022","volume":"72","author":"Siegel","year":"2022","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1093\/jnci\/djab122","article-title":"Association of the COVID-19 Pandemic with Patterns of Statewide Cancer Services","volume":"114","author":"Yabroff","year":"2022","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"172784","DOI":"10.1016\/j.ejphar.2019.172784","article-title":"Old Wine in New Bottles: Drug Repurposing in Oncology","volume":"866","author":"Antoszczak","year":"2020","journal-title":"Eur. J. Pharmacol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1111\/jphp.13273","article-title":"Drug Repositioning: A Brief Overview","volume":"72","author":"Jourdan","year":"2020","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"442","DOI":"10.3332\/ecancer.2014.485","article-title":"The Repurposing Drugs in Oncology (ReDO) Project","volume":"8","author":"Pantziarka","year":"2014","journal-title":"Ecancermedicalscience"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1007\/s12272-018-1017-3","article-title":"Antipsychotic Dopamine Receptor Antagonists, Cancer, and Cancer Stem Cells","volume":"41","author":"Roney","year":"2018","journal-title":"Arch. Pharm. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.mehy.2012.03.026","article-title":"Antipsychotic Drugs: Pro-Cancer or Anti-Cancer? A Systematic Review","volume":"79","author":"Fond","year":"2012","journal-title":"Med. Hypotheses"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e1111","DOI":"10.1038\/cddis.2014.56","article-title":"Harnessing the Lysosome-Dependent Antitumor Activity of Phenothiazines in Human Small Cell Lung Cancer","volume":"5","author":"Zong","year":"2014","journal-title":"Cell Death Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"127ra36","DOI":"10.1126\/scitranslmed.3003016","article-title":"Anti-Invasive Adjuvant Therapy with Imipramine Blue Enhances Chemotherapeutic Efficacy Against Glioma","volume":"4","author":"Munson","year":"2012","journal-title":"Sci. Transl. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"37","DOI":"10.4081\/oncol.2019.411","article-title":"Prospects for Repurposing CNS Drugs for Cancer Treatment","volume":"13","author":"Abdelaleem","year":"2019","journal-title":"Oncol. Rev."},{"key":"ref_11","first-page":"5983","article-title":"Possible Biological and Clinical Applications of Phenothiazines","volume":"37","author":"Varga","year":"2017","journal-title":"Anticancer Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"5701","DOI":"10.21873\/anticanres.11153","article-title":"The Anticancer Activity of the Old Neuroleptic Phenothiazine-Type Drug Thioridazine","volume":"36","author":"Spengler","year":"2016","journal-title":"Anticancer Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"172402","DOI":"10.1016\/j.ejphar.2019.05.031","article-title":"Molecular Mechanisms of Anti-Psychotic Drugs for Improvement of Cancer Treatment","volume":"856","author":"Hendouei","year":"2019","journal-title":"Eur. J. Pharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1002\/jat.4046","article-title":"In Vitro Anticancer Activity of Fluphenazine, Perphenazine and Prochlorperazine. A Review","volume":"41","year":"2021","journal-title":"J. Appl. Toxicol."},{"key":"ref_15","unstructured":"World Health Organization (2009). WHO Model List of Essential Medicines, WHO."},{"key":"ref_16","unstructured":"(2022, August 17). Fluphenazine: Uses, Interactions, Mechanism of Action | DrugBank Online. Available online: https:\/\/go.drugbank.com\/drugs\/DB00623."},{"key":"ref_17","first-page":"1711","article-title":"Effect of Anti-Calmodulin Drugs on the Growth and Sensitivity of C6 Rat Glioma Cells to Bleomycin","volume":"14","author":"Hait","year":"1994","journal-title":"Anticancer Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1016\/j.bbamcr.2013.10.021","article-title":"The Many Faces of Calmodulin in Cell Proliferation, Programmed Cell Death, Autophagy, and Cancer","volume":"1843","author":"Berchtold","year":"2014","journal-title":"Biochim. Biophys. Acta\u2014Mol. Cell Res."},{"key":"ref_19","unstructured":"(2022, August 18). Study of Fluphenazine in Relapsed or Relapsed-and-Refractory Multiple Myeloma\u2014Full Text View\u2014ClinicalTrials.Gov, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT00821301?term=fluphenazine&draw=2&rank=1."},{"key":"ref_20","unstructured":"(2022, August 18). Fluphenazine in Treating Patients with Refractory Advanced Multiple Myeloma\u2014Full Text View\u2014ClinicalTrials.Gov, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT00335647?term=fluphenazine&draw=2&rank=4."},{"key":"ref_21","first-page":"1111","article-title":"Effect of Fluphenazine HCl on R3230AC Mammary Carcinoma and Mammary Glands of the Rat","volume":"31","author":"Hilf","year":"1971","journal-title":"Cancer Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0162-3109(84)90051-1","article-title":"The Inhibitory Effect of Phenothiazines on NK-Mediated Cytolysis of Tumor Cells","volume":"8","author":"Laing","year":"1984","journal-title":"Immunopharmacology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"15495","DOI":"10.1021\/jp904805t","article-title":"Interactions of Dihydrochloride Fluphenazine with DPPC Liposomes: ATR-IR and 31P NMR Studies","volume":"113","author":"Szwed","year":"2009","journal-title":"J. Phys. Chem. B"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3605","DOI":"10.1021\/jp410882r","article-title":"Phase Separation in Phosphatidylcholine Membrane Caused by the Presence of a Pyrimidine Analogue of Fluphenazine with High Anti-Multidrug-Resistance Activity","volume":"118","author":"Jaszczyszyn","year":"2014","journal-title":"J. Phys. Chem. B"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"5768","DOI":"10.4049\/jimmunol.0903559","article-title":"High-Throughput Screening for TLR3-IFN Regulatory Factor 3 Signaling Pathway Modulators Identifies Several Antipsychotic Drugs as TLR Inhibitors","volume":"184","author":"Zhu","year":"2010","journal-title":"J. Immunol."},{"key":"ref_26","first-page":"332","article-title":"New Fluphenazine Analogues as Inhibitors of P-Glycoprotein in Human Lymphocyte Cultures","volume":"16","author":"Jaszczyszyn","year":"2012","journal-title":"Contemp. Oncol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.phrs.2016.05.004","article-title":"A Cell-Based Quantitative High-Throughput Image Screening Identified Novel Autophagy Modulators","volume":"110","author":"Li","year":"2016","journal-title":"Pharmacol. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"10169","DOI":"10.1038\/s41598-021-89627-0","article-title":"Drug Repurposing for Ligand-Induced Rearrangement of Sirt2 Active Site-Based Inhibitors via Molecular Modeling and Quantum Mechanics Calculations","volume":"11","author":"Bharadwaj","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Manoharan, G.B., Okutachi, S., and Abankwa, D. (2022). Potential of Phenothiazines to Synergistically Block Calmodulin and Reactivate PP2A in Cancer Cells. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0268635"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1139\/O09-058","article-title":"Calmodulin Inhibition Contributes to Sensitize TRAIL-Induced Apoptosis in Human Lung Cancer H1299 Cells","volume":"87","author":"Hwang","year":"2009","journal-title":"Biochem. Cell Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e181","DOI":"10.1038\/cddis.2011.62","article-title":"Chemosensitization by Phenothiazines in Human Lung Cancer Cells: Impaired Resolution of \u0393H2AX and Increased Oxidative Stress Elicit Apoptosis Associated with Lysosomal Expansion and Intense Vacuolation","volume":"2","author":"Zong","year":"2011","journal-title":"Cell Death Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e98921","DOI":"10.1172\/jci.insight.98921","article-title":"Repurposing Sertraline Sensitizes Non-Small Cell Lung Cancer Cells to Erlotinib by Inducing Autophagy","volume":"3","author":"Jiang","year":"2018","journal-title":"JCI Insight"},{"key":"ref_33","first-page":"105","article-title":"Structural Features Determining Activity of Phenothiazines and Related Drugs for Inhibition of Cell Growth and Reversal of Multidrug Resistance","volume":"35","author":"Ford","year":"1989","journal-title":"Mol. Pharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2055","DOI":"10.18632\/oncotarget.26725","article-title":"AXL Knockdown Gene Signature Reveals a Drug Repurposing Opportunity for a Class of Antipsychotics to Reduce Growth and Metastasis of Triple-Negative Breast Cancer","volume":"10","author":"Goyette","year":"2019","journal-title":"Oncotarget"},{"key":"ref_35","first-page":"459","article-title":"Repositioning Antipsychotic Fluphenazine Hydrochloride for Treating Triple Negative Breast Cancer with Brain Metastases and Lung Metastases","volume":"9","author":"Xu","year":"2019","journal-title":"Am. J. Cancer Res."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Duarte, D., Cardoso, A., and Vale, N. (2021). Synergistic Growth Inhibition of HT-29 Colon and MCF-7 Breast Cancer Cells with Simultaneous and Sequential Combinations of Antineoplastics and CNS Drugs. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22147408"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Duarte, D., R\u00eama, A., Amorim, I., and Vale, N. (2022). Drug Combinations: A New Strategy to Extend Drug Repurposing and Epithelial-Mesenchymal Transition in Breast and Colon Cancer Cells. Biomolecules, 12.","DOI":"10.3390\/biom12020190"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Duarte, D., Falc\u00e3o, S.I., El Mehdi, I., Vilas-Boas, M., Vale, N., El Mehdi, I., Vilas-Boas, M., and Vale, N. (2022). Honeybee Venom Synergistically Enhances the Cytotoxic Effect of CNS Drugs in HT-29 Colon and MCF-7 Breast Cancer Cell Lines. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14030511"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e2709","DOI":"10.1038\/cddis.2017.130","article-title":"Functional Inhibition of Acid Sphingomyelinase by Fluphenazine Triggers Hypoxia-Specific Tumor Cell Death","volume":"8","author":"Klutzny","year":"2017","journal-title":"Cell Death Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1016\/j.biopha.2018.06.170","article-title":"Increased Lipid Peroxidation, Apoptosis and Selective Cytotoxicity in Colon Cancer Cell Line LoVo and Its Doxorubicin-Resistant Subline LoVo\/Dx in the Presence of Newly Synthesized Phenothiazine Derivatives","volume":"106","author":"Michalak","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"\u015aroda-Pomianek, K., Michalak, K., Palko-\u0141abuz, A., Uryga, A., \u015awi\u0105tek, P., Majkowski, M., and Weso\u0142owska, O. (2019). The Combined Use of Phenothiazines and Statins Strongly Affects Doxorubicin-Resistance, Apoptosis, and Cox-2 Activity in Colon Cancer Cells. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20040955"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.tox.2015.02.004","article-title":"Cytotoxicity of Phenothiazine Derivatives Associated with Mitochondrial Dysfunction: A Structure-Activity Investigation","volume":"330","author":"Bettanin","year":"2015","journal-title":"Toxicology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1191\/096032701680350523","article-title":"Effects of the Antianginal Drug Fendiline on Ca2+ Movement in Hepatoma Cells","volume":"20","author":"Cheng","year":"2001","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1016\/j.tiv.2004.03.012","article-title":"Comparison of Alamar Blue and MTT Assays for High Through-Put Screening","volume":"18","author":"Hamid","year":"2004","journal-title":"Toxicol. In Vitro"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1016\/0006-3223(94)91145-2","article-title":"An Inhibitory Effect of Psychoactive Drugs on a Human Neuroblastoma Cell Line","volume":"35","author":"Silver","year":"1994","journal-title":"Biol. Psychiatry"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Gil-Ad, I., Offen, D., Shtaif, B., Galili-Mosberg, R., and Weizman, A. (1998). Haloperidol Induces Neurotoxicity in Mouse Embryo Brain Tissue. Progress in Alzheimer\u2019s and Parkinson\u2019s Diseases, Springer.","DOI":"10.1007\/978-1-4615-5337-3_23"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1385\/JMN:22:3:189","article-title":"Characterization of Phenothiazine-Incluced Apoptosis in Neuroblastoma and Glioma Cell Lines: Clinical Relevance and Possible Application for Brain-Derived Tumors","volume":"22","author":"Shtaif","year":"2004","journal-title":"J. Mol. Neurosci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3690","DOI":"10.1158\/1078-0432.CCR-08-2699","article-title":"Meta-Mining of Neuroblastoma and Neuroblast Gene Expression Profiles Reveals Candidate Therapeutic Compounds","volume":"15","author":"Pattyn","year":"2009","journal-title":"Clin. Cancer Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e1753","DOI":"10.1038\/cddis.2015.77","article-title":"Identification of Thioridazine, an Antipsychotic Drug, as an Antiglioblastoma and Anticancer Stem Cell Agent Using Public Gene Expression Data","volume":"6","author":"Cheng","year":"2015","journal-title":"Cell Death Dis."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Jacobs, K.A., Andr\u00e9-Gr\u00e9goire, G., Maghe, C., Thys, A., Li, Y., Harford-Wright, E., Trillet, K., Douanne, T., Alves Nicolau, C., and Fr\u00e9nel, J. (2020). Paracaspase MALT1 Regulates Glioma Cell Survival by Controlling Endo-lysosome Homeostasis. EMBO J., 39.","DOI":"10.15252\/embj.2019102030"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3973","DOI":"10.1016\/0006-2952(85)90374-0","article-title":"Characteristics of the Cytotoxic Effects of the Phenothiazine Class of Calmodulin Antagonists","volume":"34","author":"Hait","year":"1985","journal-title":"Biochem. Pharmacol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.freeradbiomed.2015.05.023","article-title":"A Subset of N-Substituted Phenothiazines Inhibits NADPH Oxidases","volume":"86","author":"Seredenina","year":"2015","journal-title":"Free Radic. Biol. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"5867","DOI":"10.21873\/anticanres.11172","article-title":"Highly Halaven-Resistant KBV20C Cancer Cells Can Be Sensitized by Co-Treatment with Fluphenazine","volume":"36","author":"Cheon","year":"2016","journal-title":"Anticancer Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"5101","DOI":"10.21873\/anticanres.12830","article-title":"Low Doses of the Anti-Psychotic Drug Aripiprazole Have Strong P-Gp-Inhibitory Activity and Sensitize Anti-Mitotic Drug-Resistant Cancer Cells","volume":"38","author":"Kim","year":"2018","journal-title":"Anticancer Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"5149","DOI":"10.21873\/anticanres.12837","article-title":"Aging-Related Repositioned Drugs, Donepezil and Sildenafil Citrate, Increase Apoptosis of Anti-Mitotic Drug-Resistant KBV20C Cells Through Different Molecular Mechanisms","volume":"38","author":"Kim","year":"2018","journal-title":"Anticancer Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"3767","DOI":"10.21873\/anticanres.13525","article-title":"Histamine Receptor Antagonists, Loratadine and Azelastine, Sensitize P-Gp-Overexpressing Antimitotic Drug-Resistant KBV20C Cells through Different Molecular Mechanisms","volume":"39","author":"Kim","year":"2019","journal-title":"Anticancer Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1196\/annals.1414.041","article-title":"Potential Inhibition of PDK1\/Akt Signaling by Phenothiazines Suppresses Cancer Cell Proliferation and Survival","volume":"1138","author":"Choi","year":"2008","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_58","first-page":"107","article-title":"Phenothiazines Induce Apoptosis in a B16 Mouse Melanoma Cell Line and Attenuate in Vivo Melanoma Tumor Growth","volume":"15","author":"Shtaif","year":"2006","journal-title":"Oncol. Rep."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1038\/bjc.2017.200","article-title":"Modulating Cancer Cell Survival by Targeting Intracellular Cholesterol Transport","volume":"117","author":"Kuzu","year":"2017","journal-title":"Br. J. Cancer"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"105295","DOI":"10.1016\/j.phrs.2020.105295","article-title":"Repurposing of Antipsychotic Trifluoperazine for Treating Brain Metastasis, Lung Metastasis and Bone Metastasis of Melanoma by Disrupting Autophagy Flux","volume":"163","author":"Xia","year":"2021","journal-title":"Pharmacol. Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2232","DOI":"10.1039\/c9pp00023b","article-title":"The Neuroleptic Drug Fluphenazine Induces a Significant UVA-Mediated Cytotoxic Effect on Three Human Cancer Cell Lines through Apoptosis","volume":"18","author":"Menilli","year":"2019","journal-title":"Photochem. Photobiol. Sci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1186\/s13045-020-00990-3","article-title":"Targeting the Wnt\/\u03b2-Catenin Signaling Pathway in Cancer","volume":"13","author":"Zhang","year":"2020","journal-title":"J. Hematol. Oncol."},{"key":"ref_63","first-page":"2319","article-title":"The Akt Pathway in Oncology Therapy and beyond (Review)","volume":"53","author":"Nitulescu","year":"2018","journal-title":"Int. J. Oncol."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Davis, C. (2007). Fluphenazine. xPharm: The Comprehensive Pharmacology Reference, Elsevier.","DOI":"10.1016\/B978-008055232-3.61772-6"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/12\/10\/1360\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:38:24Z","timestamp":1760143104000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/12\/10\/1360"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,23]]},"references-count":64,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["biom12101360"],"URL":"https:\/\/doi.org\/10.3390\/biom12101360","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,23]]}}}