Association between Thioridazine Use and Cancer Risk in Adult Patients with Schizophrenia-A Population-Based Study
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Objective Several cell line studies have demonstrated thioridazine’s anticancer, multidrug resistance-reversing and apoptosis-inducing properties in various tumors. We conducted this nationwide population-based study to investigate the association between thioridazine use and cancer risk among adult patients with schizophrenia. Methods Based on the Psychiatric Inpatient Medical Claim of the National Health Insurance Research Database of Taiwan, a total of 185,689 insured psychiatric patients during 2000 to 2005 were identified. After excluding patients with prior history of schizophrenia, only 42,273 newly diagnosed patients were included. Among them, 1,631 patients ever receiving thioridazine for more than 30 days within 6 months were selected and paired with 6,256 randomly selected non-thioridazine controls. These patients were traced till 2012/12/31 to see if they have any malignancy. Results The incidence rates of hypertension and cerebrovascular disease were higher among cases than among matched controls. The incidence of hyperlipidemia, coronary artery disease and chronic pulmonary disease did not differ between the two groups. By using Cox proportional hazard model for cancer incidence, the crude hazard ratio was significantly higher in age, hypertension, hyperlipidemia, cerebrovascular disease, coronary artery disease and chronic pulmornary disease. However, after adjusting for other covariates, only age and hypertension remained significant. Thioridazine use in adult patients with schizophrenia had no significant association with cancer. Conclusion Despite our finding that thioridazine use had no prevention in cancer in adult patients with schizophrenia. Based on the biological activity, thioridazine is a potential anticancer drug and further investigation in human with cancer is warranted.
Abstract
Objective Several cell line studies have demonstrated thioridazine’s anticancer, multidrug resistance-reversing and apoptosis-inducing properties in various tumors. We conducted this nationwide population-based study to investigate the association between thioridazine use and cancer risk among adult patients with schizophrenia. Methods Based on the Psychiatric Inpatient Medical Claim of the National Health Insurance Research Database of Taiwan, a total of 185,689 insured psychiatric patients during 2000 to 2005 were identified. After excluding patients with prior history of schizophrenia, only 42,273 newly diagnosed patients were included. Among them, 1,631 patients ever receiving thioridazine for more than 30 days within 6 months were selected and paired with 6,256 randomly selected non-thioridazine controls. These patients were traced till 2012/12/31 to see if they have any malignancy. Results The incidence rates of hypertension and cerebrovascular disease were higher among cases than among matched controls. The incidence of hyperlipidemia, coronary artery disease and chronic pulmonary disease did not differ between the two groups. By using Cox proportional hazard model for cancer incidence, the crude hazard ratio was significantly higher in age, hypertension, hyperlipidemia, cerebrovascular disease, coronary artery disease and chronic pulmornary disease. However, after adjusting for other covariates, only age and hypertension remained significant. Thioridazine use in adult patients with schizophrenia had no significant association with cancer. Conclusion Despite our finding that thioridazine use had no prevention in cancer in adult patients with schizophrenia. Based on the biological activity, thioridazine is a potential anticancer drug and further investigation in human with cancer is warranted.
참고문헌 (24)
- Nagel D, "Pharmacologic inhibition of MALT1 protease by phenothiazines as a therapeutic approach for the treatment of aggressive ABC-DLBCL", Cancer Cell, 22, pp.825~837 (2012)
- Byun HJ, "Anti-angiogenic effects of thioridazine involving the FAK-mTOR pathway", Microvasc Res, 84, pp.227~234 (2012)
- Park MS, "Thioridazine inhibits angiogenesis and tumor growth by targeting the VEGFR-2", PI3K, Oncotarget, pp.2014, 5[DOI]
- Kang S, "Thioridazine induces apoptosis by targeting the PI3K", Akt, Apoptosis, pp.2012, 17[DOI]
- Mu J, "Thioridazine, an antipsychotic drug, elicits potent antitumor effects in gastric cancer", Oncol Rep, 31, pp.2107~2114 (2014)
- Strobl JS, "Inhibition of human breast cancer cell proliferation in tissue culture by the neuroleptic agents pimozide and thioridazine", Cancer Res, 50, pp.5399~5405 (1990)
- Gil-Ad I, "Phenothiazines induce apoptosis in a B16 mouse melanoma cell line and attenuate in vivo melanoma tumor growth", Oncol Rep, 15, pp.107~112 (2006)
- Zhelev Z, "Phenothiazines suppress proliferation and induce apoptosis in cultured leukemic cells without any influence on the viability of normal lymphocytes. Phenothiazines and leukemia", Cancer Chemother Pharmacol, 53, pp.267~275 (2004)
- Rho SB, "A gene signature-based approach identifies thioridazine as an inhibitor of phosphatidylinositol-3'-kinase (PI3K)", AKT pathway in ovarian cancer cells, 2011, pp.120, 121~127
- Spengler G, "The aticancer activity of the old neuroleptic phenothiazine-type drug thioridazine", Anticancer Res, 36, pp.5701~5706 (2016)
- Meng Q, "The important application of thioridazine in the endometrial cancer", Am J Transl Res, 8, pp.2767~2775 (2016)
- Yue H, "Targeting lung cancer stem cells with antipsychological drug thioridazine", Biomed Res Int, 2016, pp.6709828~ (2016)
- Shen J, "Thioridazine has potent antitumor effects on lung cancer stem-like cells", Oncol Lett, 13, pp.1563~1568 (2017)
- Zhang C, "Thioridazine elicits potent antitumor effects in colorectal cancer stem cells", Oncol Rep, 37, pp.1168~1174 (2017)
- Spengler G, "Thioridazine induces apoptosis of multidrug-resistant mouse lymphoma cells transfected with the human ABCB1 and inhibits the expression of P-glycoprotein", Anticancer Res, 31, pp.4201~4205 (2011)
- Chou FH, "The incidence and relative risk factors for developing cancer among patients with schizophrenia: a nine-year follow-up study", Schizophr Res, 129, pp.97~103 (2011)
- Yde CW, "The antipsychotic drug chlorpromazine enhances the cytotoxic effect of tamoxifen in tamoxifen-sensitive and tamoxifen-resistant human breast cancer cells", Anticancer Drugs, 20, pp.723~735 (2009)
- Rybakowski JK, "Functional polymorphism of the matrix metalloproteinase-9 (MMP-9) gene in schizophrenia", Schizophr Res, 109, pp.90~93 (2009)
- Stocks T, "Blood pressure and risk of cancer incidence and mortality in the Metabolic Syndrome and Cancer Project", Hypertension, 59, pp.802~810 (2012)
- Radisauskas R, "Hypertension, serum lipids and cancer risk: A review of epidemiological evidence", Medicina (Kaunas), 52, pp.89~98 (2016)
- Largent JA, "Hypertension, antihypertensive medication use, and breast cancer risk in the California Teachers Study cohort", Cancer Causes Control, 21, pp.1615~1624 (2010)
- Campisi J., "Aging, cellular senescence, and cancer", Annu Rev Physiol, 75, pp.685~705 (2013)
- Seo SU, "Thioridazine enhances sensitivity to carboplatin in human head and neck cancer cells through downregulation of c-FLIP and Mcl-1 expression", Cell Death Dis, 8 (2017)
- Jin X, "Codelivery of thioridazine and doxorubicin using nanoparticles for effective breast cancer therapy", Int J Nanomedicine, 11, pp.4545~4552 (2016)