The Relationship between Antipsychotic Medications and Various Cancers: A Review Article
Keywords:Antipsychotic Agents, Neoplasms, Medication Therapy Management
Background: Cancer is a global problem and causes lots of deaths across the world. Due to the high cost of manufacturing and developing new drugs, there is more willingness to use medications that may have anti-neoplastic effects.
Objectives: Antipsychotic drugs have a long history of clinical use. Currently, there are various reports about the anti-cancer effects of antipsychotic drugs in different types of malignancies.
Methods: In this study, the effects and mechanisms of several antipsychotic drugs on different types of cancer were investigated. Conducting Research Literature Reviews, some antipsychotic drugs can inhibit the proliferation of cancer cells and some others can be used to ease the symptoms caused by cancer.
Results: Certainly, the anticancer effects of all antipsychotic drugs haven’t been thoroughly investigated and it is reported that few drugs may reverse the effects and increase the risk of neoplasm.
Conclusions: Nevertheless, it is clear that some antipsychotic drugs can be considered as cancer therapy medications because of their beneficial effects.
Huang J, Zhao D, Liu Z, Liu F. Repurposing psychiatric drugs as anti-cancer agents. Cancer letters. 2018;419:257-6510.1016/j. canlet.2018. 01. 058.
Sak K. Chemotherapy and dietary phytochemical agents. Chemotherapy research and practice. 2012;2012:28257010.1155/2012/282570.
Thanacoody HKR. Thioridazine: resurrection as an antimicrobial agent? British journal of clinical pharmacology. 2007;64:566-7410.1111/j.1365-2125.2007.03021.x.
Mortensen PB. Neuroleptic medication and reduced risk of prostate cancer in schizophrenic patients. Acta Psychiatrica Scandinavica. 1992;85:390-3
Mortensen PB. The incidence of cancer in schizophrenic patients. Journal of epidemiology and community health. 1989;43:43-7
Lichtermann D, Ekelund J, Pukkala E, Tanskanen A, Lonnqvist J. Incidence of cancer among persons with schizophrenia and their relatives. Archives of general psychiatry. 2001;58:573-8
Chen JJ, Cai N, Chen GZ, Jia CC, Qiu DB, Du C, et al. The neuroleptic drug pimozide inhibits stem-like cell maintenance and tumorigenicity in hepatocellular carcinoma. Oncotarget. 2017;8: 17593- 60910.18632/ oncotarget.4307.
Marder SR, McQuade RD, Stock E, Kaplita S, Marcus R, Safferman AZ, et al. Aripiprazole in the treatment of schizophrenia: safety and tolerability in short-term, placebo-controlled trials. Schizophrenia research. 2003;61:123-36
Boettger S, Breitbart W. An open trial of aripiprazole for the treatment of delirium in hospitalized cancer patients. Palliative & supportive care. 2011;9:351-710.1017/ s1478951511000368.
Burris KD, Molski TF, Xu C, Ryan E, Tottori K, Kikuchi T, et al. Aripiprazole, a novel antipsychotic, is a high-affinity partial agonist at human dopamine D2 receptors. The Journal of pharmacology and experimental therapeutics. 2002;302:381-9
Suzuki S, Okada M, Kuramoto K, Takeda H, Sakaki H, Watarai H, et al. Aripiprazole, an Antipsychotic and Partial Dopamine Agonist, Inhibits Cancer Stem Cells and Reverses Chemoresistance. Anticancer research. 2016;36:5153-6110.21873/ anticanres. 11085.
Nagasaka Y, Sano T, Oda K, Kawamura A, Usui T. Impact of genetic deficiencies of P-glycoprotein and breast cancer resistance protein on pharmacokinetics of aripiprazole and dehydroaripiprazole. Xenobiotica. 2014;44:926-32
Hendouei N, Saghafi F, Shadfar F, Hosseinimehr SJ. Molecular mechanisms of anti-psychotic drugs for improvement of cancer treatment. European journal of pharmacology. 2019;856: 172402
Yong M, Yu T, Tian S, Liu S, Xu J, Hu J, et al. DR2 blocker thioridazine: A promising drug for ovarian cancer therapy. Oncology letters. 2017;14:8171-710.3892/ol.2017.7184.
Chen MH, Yang WL, Lin KT, Liu CH, Liu YW, Huang KW, et al. Gene expression-based chemical genomics identifies potential therapeutic drugs in hepatocellular carcinoma. PloS one. 2011;6:e2718610.1371/journal.pone.0027186.
Zhelev Z, Ohba H, Bakalova R, Hadjimitova V, Ishikawa M, Shinohara Y, et al. Phenothiazines suppress proliferation and induce apoptosis in cultured leukemic cells without any influence on the viability of normal lymphocytes. Phenothiazines and leukemia. Cancer chemotherapy and pharmacology. 2004;53:267-7510.1007/s00280-003-0738-1.
Shin SY, Kim CG, Kim SH, Kim YS, Lim Y, Lee YH. Chlorpromazine activates p21Waf1/Cip1 gene transcription via early growth response-1 (Egr-1) in C6 glioma cells. Experimental & molecular medicine. 2010;42:395-40510.3858/emm. 2010.42. 5. 041.
Lee WY, Lee WT, Cheng CH, Chen KC, Chou CM, Chung CH, et al. Repositioning antipsychotic chlorpromazine for treating colorectal cancer by inhibiting sirtuin 1. Oncotarget. 2015;6:27580-9510.18632/oncotarget.4768.
Darkin S, McQuillan J, Ralph R. Chlorpromazine: a potential anticancer agent? Biochemical and biophysical research communications. 1984;125: 184-91
Shin SY, Choi BH, Ko J, Kim SH, Kim YS, Lee YH. Clozapine, a neuroleptic agent, inhibits Akt by counteracting Ca2+/calmodulin in PTEN-negative U-87MG human glioblastoma cells. Cellular signaling. 2006;18:1876-86
Hendouei N, Hosseini SH, Panahi A, Khazaeipour Z, Barari F, Sahebnasagh A, et al. Negative correlation between serum S100B and Leptin levels in schizophrenic patients during treatment with clozapine and risperidone: preliminary evidence. Iranian Journal of pharmaceutical research: IJPR. 2016;15:323
Rajagopal S. Clozapine, agranulocytosis, and benign ethnic neutropenia. Postgrad Med J. 2005;81:545-610.1136/pgmj.2004.031161.
Nielsen J, Boysen A. Clozapine treatment associated with increased risk of acute myeloid leukemia (AML). Schizophrenia research. 2010;123:270-210.1016/j.schres.2010.08.035.
Cheon JH, Lee BM, Kim HS, Yoon S. Highly Halaven-resistant KBV20C Cancer Cells Can Be Sensitized by Co-treatment with Fluphenazine. Anticancer research. 2016;36:5867-7410.21873/ anticanres. 11172.
Jaszczyszyn A, Gasiorowski K, Swiatek P, Malinka W, Cieslik-Boczula K, Petrus J, et al. New fluphenazine analogs as inhibitors of P-glycoprotein in human lymphocyte cultures. Contemporary oncology (Poznan, Poland). 2012;16:332-710.5114/wo.2012.30063.
Menilli L, Garcia-Argaez AN, Dalla Via L, Miolo G. The neuroleptic drug fluphenazine induces a significant UVA-mediated cytotoxic effect on three human cancer cell lines through apoptosis. Photochemical & photobiological sciences: Official journal of the European Photochemistry Association and the European Society for Photobiology. 201910.1039/c9pp00023b.
Shi XN, Li H, Yao H, Liu X, Li L, Leung KS, et al. In Silico Identification and In Vitro and In Vivo Validation of Anti-Psychotic Drug Fluspirilene as a Potential CDK2 Inhibitor and a Candidate Anti-Cancer Drug. PloS one. 2015;10:e013207210.1371/ journal.pone.0132072.
Patil SP, Pacitti MF, Gilroy KS, Ruggiero JC, Griffin JD, Butera JJ, et al. Identification of antipsychotic drug fluspirilene as a potential p53-MDM2 inhibitor: a combined computational and experimental study. Journal of computer-aided molecular design. 2015;29:155-6310.1007/s10822-014-9811-6.
Bai T, Wang S, Zhao Y, Zhu R, Wang W, Sun Y. Haloperidol, a sigma receptor 1 antagonist, promotes ferroptosis in hepatocellular carcinoma cells. Biochem Biophys Res Commun. 2017; 491:919-2510.1016/j.bbrc.2017.07.136.
Olivieri M, Amata E, Vinciguerra S, Fiorito J, Giurdanella G, Drago F, et al. Antiangiogenic Effect of (±)-haloperidol metabolite ii valproate ester [(±)-MRJF22] in human microvascular retinal endothelial cells. Journal of medicinal chemistry. 2016;59:9960-6
Flank J, Schechter T, Gibson P, Johnston DL, Orsey AD, Portwine C, et al. Olanzapine for prevention of chemotherapy-induced nausea and vomiting in children and adolescents: a multi-center, feasibility study. Supportive care in cancer: official journal of the Multinational Association of Supportive Care in Cancer. 2018;26:549-5510.1007/s00520-017-3864-8.
Hocking CM, Kichenadasse G. Olanzapine for chemotherapy-induced nausea and vomiting: a systematic review. Supportive care in cancer: official journal of the Multinational Association of Supportive Care in Cancer. 2014;22:1143-5110. 1007/s00520-014-2138-y.
Rahman T, Clevenger CV, Kaklamani V, Lauriello J, Campbell A, Malwitz K, et al. Antipsychotic treatment in breast cancer patients. American Journal of Psychiatry. 2014;171:616-21
Sanomachi T, Suzuki S, Kuramoto K, Takeda H, Sakaki H, Togashi K, et al. Olanzapine, an Atypical Antipsychotic, Inhibits Survivin Expression and Sensitizes Cancer Cells to Chemotherapeutic Agents. Anticancer research. 2017;37:6177-8810.21873/anticanres.12067.
Ranjan A, Srivastava SK. Penfluridol suppresses glioblastoma tumor growth by Akt-mediated inhibition of GLI1. Oncotarget. 2017;8:32960-7610.18632/oncotarget.16515.
Sleire L, Forde HE, Netland IA, Leiss L, Skeie BS, Enger PO. Drug repurposing in cancer. Pharmacological research. 2017;124:74-9110.1016/ j.phrs.2017.07.013.
Ranjan A, Gupta P, Srivastava SK. Penfluridol: An Antipsychotic Agent Suppresses Metastatic Tumor Growth in Triple-Negative Breast Cancer by Inhibiting Integrin Signaling Axis. Cancer research. 2016;76:877-9010.1158/0008-5472.Can-15-1233.
Tecott LH, Kwong LL, Uhr S, Peroutka SJ. Differential modulation of dopamine D2 receptors by chronic haloperidol, nitrendipine, and pimozide. Biological psychiatry. 1986;21:1114-22
Dakir EH, Pickard A, Srivastava K, McCrudden CM, Gross SR, Lloyd S, et al. The anti-psychotic drug pimozide is a novel chemotherapeutic for breast cancer. Oncotarget. 2018;9:34889-91010.18632/ oncotarget. 26175.
Fako V, Yu Z, Henrich CJ, Ransom T, Budhu AS, Wang XW. Inhibition of wnt/beta-catenin Signaling in Hepatocellular Carcinoma by an Antipsychotic Drug Pimozide. International journal of biological sciences. 2016;12:768-7510.7150/ijbs.14718.
Gupta MA, Vujcic B, Pur DR, Gupta AK. Use of antipsychotic drugs in dermatology. Clinics in dermatology. 2018;36:765-7310.1016/j. clindermatol. 2018. 08.006.
Wang H, Shen W, Hu X, Zhang Y, Zhuo Y, Li T, et al. Quetiapine inhibits osteoclastogenesis and prevents human breast cancer-induced bone loss through suppression of the RANKL-mediated MAPK and NF-kappaB signaling pathways. Breast cancer research and treatment. 2015;149:705-1410.1007/s10549-015-3290-x.
Pasquini M, Speca A, Biondi M. Quetiapine for tamoxifen-induced insomnia in women with breast cancer. Psychosomatics. 2009;50:159-6110.1176/appi.psy.50.2.159.
Wang Y, Huang N, Li H, Liu S, Chen X, Yu S, et al. Promoting oligodendroglial-oriented differentiation of glioma stem cell: a repurposing of quetiapine for the treatment of malignant glioma. Oncotarget. 2017;8:37511-2410. 18632/oncotarget.16400.
Yeh WL, Lin HY, Wu HM, Chen DR. Combination treatment of tamoxifen with risperidone in breast cancer. PloS one. 2014;9:e9880510.1371/ journal.pone.0098805.
Dilly SJ, Clark AJ, Marsh A, Mitchell DA, Cain R, Fishwick CWG, et al. A chemical genomics approach to drug reprofiling in oncology: Antipsychotic drug risperidone as a potential adenocarcinoma treatment. Cancer letters. 2017;393:16-2110.1016/j.canlet.2017.01.042.
Wang JS, Zhu HJ, Markowitz JS, Donovan JL, Yuan HJ, DeVane CL. Antipsychotic drugs inhibit the function of breast cancer resistance protein. Basic & clinical pharmacology & toxicology. 2008; 103:336-41
Reutfors J, Wingard L, Brandt L, Wang Y, Qiu H, Kieler H, et al. Risk of breast cancer in risperidone users: A nationwide cohort study. Schizophrenia research. 2017;182:98-10310.1016/ j.schres.2016.10.035.
Lai EC, Chang CH, Kao Yang YH, Lin SJ, Lin CY. Effectiveness of sulpiride in adult patients with schizophrenia. Schizophrenia bulletin. 2013;39:673-8310.1093/schbul/sbs002.
Li J, Yao QY, Xue JS, Wang LJ, Yuan Y, Tian XY, et al. Dopamine D2 receptor antagonist sulpiride enhances dexamethasone responses in the treatment of drug-resistant and metastatic breast cancer. Acta pharmacologica Sinica. 2017;38:1282-9610.1038/aps.2017.24.
Kang S, Dong SM, Kim BR, Park MS, Trink B, Byun HJ, et al. Thioridazine induces apoptosis by targeting the PI3K/Akt/mTOR pathway in cervical and endometrial cancer cells. Apoptosis: an international journal on programmed cell death. 2012;17:989-9710.1007/s10495-012-0717-2.
Park MS, Dong SM, Kim BR, Seo SH, Kang S, Lee EJ, et al. Thioridazine inhibits angiogenesis and tumor growth by targeting the VEGFR-2/PI3K/mTOR pathway in ovarian cancer xenografts. Oncotarget. 2014;5:4929-3410.18632/ oncotarget.2063.
Yue H, Huang D, Qin L, Zheng Z, Hua L, Wang G, et al. Targeting Lung Cancer Stem Cells with Antipsychological Drug Thioridazine. BioMed research international. 2016;2016:670982810. 1155/ 2016/6709828.
Spengler G, Csonka A, Molnar J, Amaral L. The Anticancer Activity of the Old Neuroleptic Phenothiazine-type Drug Thioridazine. Anticancer research. 2016;36:5701-610.21873/ anticanres. 11153.
Mu J, Xu H, Yang Y, Huang W, Xiao J, Li M, et al. Thioridazine, an antipsychotic drug, elicits potent antitumor effects in gastric cancer. Oncology reports. 2014;31:2107-1410.3892/or. 2014.3068.
Polischouk AG, Holgersson A, Zong D, Stenerlow B, Karlsson HL, Moller L, et al. The antipsychotic drug trifluoperazine inhibits DNA repair and sensitizes non small cell lung carcinoma cells to DNA double-strand break induced cell death. Molecular cancer therapeutics. 2007;6:2303-910. 1158/ 1535-7163.Mct-06-0402.
Ganapathi R, Grabowski D. Enhancement of sensitivity to adriamycin in resistant P388 leukemia by the calmodulin inhibitor trifluoperazine. Cancer research. 1983;43:3696-9
Perez RP, Handel LM, Hamilton TC. Potentiation of cisplatin cytotoxicity in human ovarian carcinoma cell lines by trifluoperazine, a calmodulin inhibitor. Gynecologic oncology. 1992;46:82-7
Gangopadhyay S, Karmakar P, Dasgupta U, Chakraborty A. Trifluoperazine stimulates ionizing radiation-induced cell killing through inhibition of DNA repair. Mutation research. 2007;633:117-2510.1016/j.mrgentox.2007.05.011.
How to Cite
Copyright (c) 2020 Critical Comments in Biomedicine
This work is licensed under a Creative Commons Attribution 4.0 International License.