Targeting the cellular schizophrenia. Likely employment of the antipsychotic agent pimozide in treatment of refractory cancers and glioblastoma

Critical Reviews in Oncology/Hematology

Volumn 128, Issue , 2018, Pages 96-109

  Elmaci, Ilhan ^a   Altinoz, Meric A ^b,c  

^a Neuroacademy Group   (Turkey)

^b Neurooncology Branch   (Turkey)

^c MAASTRICHT UNIVERSITY   (Netherlands)

Author keywords

Glioblastoma; Pimozide; Refractory cancers

Indexed keywords

BETA CATENIN; CALCIUM CHANNEL T TYPE; CALMODULIN; CHOLESTEROL; DELTA OPIATE RECEPTOR; DEUBIQUITINASE; DNA; DOPAMINE 2 RECEPTOR; FATTY ACID BINDING PROTEIN 4; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; PIMOZIDE; SEROTONIN 7 RECEPTOR; STAT3 PROTEIN; STAT5 PROTEIN; TRANSLATIONALLY CONTROLLED TUMOR PROTEIN; TUMOR PROTEIN; UBIQUITIN SPECIFIC PROTEASE 1; UNCLASSIFIED DRUG; WNT PROTEIN; ANTINEOPLASTIC AGENT; NEUROLEPTIC AGENT;

ANTINEOPLASTIC ACTIVITY; AUTOPHAGY; BREAST CANCER; CACHEXIA; CANCER INHIBITION; CANCER STEM CELL; CANCER THERAPY; DNA DAMAGE; DRUG STRUCTURE; DRUG TARGETING; ENZYME INHIBITION; GLIOBLASTOMA; HUMAN; LEUKEMIA; LIVER CELL CARCINOMA; LUNG CANCER; MALIGNANT NEOPLASM; MELANOMA; NEUROBLASTOMA; NONHUMAN; PANCREAS CANCER; PROSTATE CANCER; PROTEIN EXPRESSION; REFRACTORY CANCER; REVIEW; ANIMAL; DRUG EFFECT; DRUG RESISTANCE; NEOPLASM; SCHIZOPHRENIA; SIGNAL TRANSDUCTION;

ANIMALS; ANTINEOPLASTIC AGENTS; ANTIPSYCHOTIC AGENTS; DRUG RESISTANCE, NEOPLASM; GLIOBLASTOMA; HUMANS; NEOPLASMS; PIMOZIDE; SCHIZOPHRENIA; SIGNAL TRANSDUCTION;

EID: 85048558766     PISSN: 10408428     EISSN: 18790461     Source Type: Journal    
DOI: 10.1016/j.critrevonc.2018.06.004     Document Type: Review

References (58)

1. Altinoz, M.A., Gedikoglu, G., Sav, A., Ozcan, E., Ozdilli, K., Bilir, A., Del Maestro, R.F., Medroxyprogesterone acetate induces c6 glioma chemosensitization via antidepressant-like lysosomal phospholipidosis/myelinosis in vitro. Int. J. Neurosci. 117:10 (2007), 1465–1480.
2. Altinoz, M.A., Guloksuz, S., Elmaci, I., Rabies virus vaccine as an immune adjuvant against cancers and glioblastoma: new studies may resurrect a neglected potential. Clin. Transl. Oncol. 19:7 (2017), 785–792.
3. Amson, R., Pece, S., Lespagnol, A., Vyas, R., Mazzarol, G., Tosoni, D., Colaluca, I., Viale, G., Rodrigues-Ferreira, S., Wynendaele, J., Chaloin, O., Hoebeke, J., Marine, J.C., Di Fiore, P.P., Telerman, A., Reciprocal repression between P53 and TCTP. Nat. Med. 18:1 (2011), 91–99.
4. Awouters, F.H., Lewi, P.J., Forty years of antipsychotic drug research—from haloperidol to paliperidone–with Dr. Paul janssen. Arzneimittelforschung 57:10 (2007), 625–632.
5. Bar-Natan, M., Nelson, E.A., Walker, S.R., Kuang, Y., Distel, R.J., Frank, D.A., Dual inhibition of Jak2 and STAT5 enhances killing of myeloproliferative neoplasia cells. Leukemia 26:6 (2012), 1407–1410.
6. Beluzi, M., Peres, S.B., Henriques, F.S., Sertié, R.A., Franco, F.O., Santos, K.B., Knobl, P., Andreotti, S., Shida, C.S., Neves, R.X., Farmer, S.R., Seelaender, M., Lima, F.B., Batista, M.L. Jr, Pioglitazone treatment increases survival and prevents body weight loss in tumor-bearing animals: possible anti-cachectic effect. PLoS One, 10(3), 2015, e0122660, 10.1371/journal.pone.0122660.
7. Bertolesi, G.E., Shi, C., Elbaum, L., Jollimore, C., Rozenberg, G., Barnes, S., Kelly, M.E., The Ca(2+) channel antagonists mibefradil and pimozide inhibit cell growth via different cytotoxic mechanisms. Mol. Pharmacol. 62:2 (2002), 210–219.
8. Boia-Ferreira, M., Basílio, A.B., Hamasaki, A.E., Matsubara, F.H., Appel, M.H., Da Costa, C.R.V., Amson, R., Telerman, A., Chaim, O.M., Veiga, S.S., Senff-Ribeiro, A., TCTP as a therapeutic target in melanoma treatment. Br J. Cancer 117:5 (2017), 656–665.
9. Chen, J., Dexheimer, T.S., Ai, Y., Liang, Q., Villamil, M.A., Inglese, J., Maloney, D.J., Jadhav, A., Simeonov, A., Zhuang, Z., Selective and cell-active inhibitors of the USP1/UAF1 deubiquitinase complex reverse cisplatin resistance in non-small cell lung cancer cells. Chem. Biol. 18:11 (2011), 1390–1400.
10. Chen, J.J., Cai, N., Chen, G.Z., Jia, C.C., Qiu, D.B., Du, C., Liu, W., Yang, Y., Long, Z.J., Zhang, Q., The neuroleptic drug pimozide inhibits stem-like cell maintenance and tumorigenicity in hepatocellular carcinoma. Oncotarget. 8:11 (2017), 17593–17609.
11. Chung, J., Irwin, M.S., Targeting the p53-family in cancer and chemosensitivity: triple threat. Curr. Drug. Targets 11:6 (2010), 667–681.
12. Covell, D.G., Integrating constitutive gene expression and chemoactivity: mining the NCI60 anticancer screen. PLoS One, 7(10), 2012, e44631, 10.1371/journal.pone.0044631.
13. Deng, P., Haynes, C.M., Mitochondrial dysfunction in cancer: potential roles of ATF5 and the mitochondrial UPR. Semin Cancer Biol., 2017, 10.1016/j.semcancer.2017.05.002 pii: S1044-579X(17)30125-6.
14. Driscoll, M.S., Rothe, M.J., Grant-Kels, J.M., Hale, M.S., Delusional parasitosis: a dermatologic, psychiatric, and pharmacologic approach. J. Am. Acad. Dermatol. 29:6 (1993), 1023–1033.
15. Fako, V., Yu, Z., Henrich, C.J., Ransom, T., Budhu, A.S., Wang, X.W., Inhibition of wnt/β-catenin signaling in hepatocellular carcinoma by an antipsychotic drug pimozide. Int. J. Biol. Sci. 12:April 7 (2016), 768–775.
16. Fortney, K., Griesman, J., Kotlyar, M., Pastrello, C., Angeli, M., Sound-Tsao, M., Jurisica, I., Prioritizing therapeutics for lung cancer: an integrative meta-analysis of cancer gene signatures and chemogenomic data. PLoS Comput. Biol., 11(March 3), 2015, e1004068, 10.1371/journal.pcbi.1004068.
17. García-Santisteban, I., Peters, G.J., Giovannetti, E., Rodríguez, J.A., USP1 deubiquitinase: cellular functions, regulatory mechanisms and emerging potential as target in cancer therapy. Mol. Cancer, 12:91(Aug 10), 2013, 10.1186/1476-4598-12-91.
18. Girardi, T., Vereecke, S., Sulima, S.O., Khan, Y., Fancello, L., Briggs, J.W., Schwab, C., de Beeck, J.O., Verbeeck, J., Royaert, J., Geerdens, E., Vicente, C., Bornschein, S., Harrison, C.J., Meijerink, J.P., Cools, J., Dinman, J.D., Kampen, K.R., De Keersmaecker, K., The t-cell leukemia associated ribosomal RPL10 R98S mutation enhances JAK-STAT signaling. Leukemia, 2017, 10.1038/leu.2017.225.
19. Gould, R.J., Murphy, K.M., Reynolds, I.J., Snyder, S.H., Antischizophrenic drugs of the diphenylbutylpiperidine type act as calcium channel antagonists. Proc. Natl. Acad. Sci. U. S. A. 80:16 (1983), 5122–5125.
20. Jandaghi, P., Najafabadi, H.S., Bauer, A.S., Papadakis, A.I., Fassan, M., Hall, A., Monast, A., von Knebel Doeberitz, M., Neoptolemos, J.P., Costello, E., Greenhalf, W., Scarpa, A., Sipos, B., Auld, D., Lathrop, M., Park, M., Büchler, M.W., Strobel, O., Hackert, T., Giese, N.A., Zogopoulos, G., Sangwan, V., Huang, S., Riazalhosseini, Y., Hoheisel, J.D., Expression of DRD2 is increased in human pancreatic ductal adenocarcinoma and inhibitors slow tumor growth in mice. Gastroenterology 151:6 (2016), 1218–1231.
21. Jiang, F., Zhang, Z., Zhang, Y., Pan, X., Yu, L., Liu, S., L-carnitine ameliorates cancer cachexia in mice partly via the carnitine palmitoyltransferase-associated PPAR-γ signaling pathway. Oncol. Res. Treat. 38:10 (2015), 511–516.
22. Kast, R.E., Glioblastoma chemotherapy adjunct via potent serotonin receptor-7 inhibition using currently marketed high-affinity antipsychotic medicines. Br. J. Pharmacol. 161:3 (2010), 481–487.
23. Kennedy, K.A., Hait, W.N., Lazo, J.S., Chemical modulation of bleomycin induced toxicity. Int. J. Radiat. Oncol. Biol Phys. 12:8 (1986), 1367–1370.
24. Kongsamut, S., Kang, J., Chen, X.L., Roehr, J., Rampe, D., A comparison of the receptor binding and HERG channel affinities for a series of antipsychotic drugs. Eur J. Pharmacol. 450:1 (2002), 37–41.
25. Kopecky, B.J., Liang, R., Bao, J., T-type calcium channel blockers as neuroprotective agents. Pflugers Arch. 466:4 (2014), 757–765.
26. Krummel, T.M., Neifeld, J.P., Taub, R.N., Effects of dopamine agonists and antagonists on murine melanoma: correlation with dopamine binding activity. Cancer 49:6 (1982), 1178–1184.
27. Lazo, J.S., Chen, D.L., Gallicchio, V.S., Hait, W.N., Increased lethality of calmodulin antagonists and bleomycin to human bone marrow and bleomycin-resistant malignant cells. Cancer Res. 46:5 (1986), 2236–2240.
28. Lee, G.L., Hait, W.N., Inhibition of growth of C6 astrocytoma cells by inhibitors of calmodulin. Life Sci. 36:4 (1985), 347–354.
29. Lee, J.K., Chang, N., Yoon, Y., Yang, H., Cho, H., Kim, E., Shin, Y., Kang, W., Oh, Y.T., Mun, G.I., Joo, K.M., Nam, D.H., Lee, J., USP1 targeting impedes GBM growth by inhibiting stem cell maintenance and radioresistance. Neuro Oncol. 18:1 (2016), 37–47.
30. Levy, J.M.M., Towers, C.G., Thorburn, A., Targeting autophagy in cancer. Nat. Rev. Cancer 17:9 (2017), 528–542.
31. McGrath, P.C., Neifeld, J.P., Inhibition of murine neuroblastoma growth by dopamine antagonists. J. Surg. Res. 36:5 (1984), 413–419.
32. McGrath, P.C., Neifeld, J.P., Inhibition of human neuroblastoma by dopamine antagonists. Surgery 98:2 (1985), 135–142.
33. Mistry, H., Hsieh, G., Buhrlage, S.J., Huang, M., Park, E., Cuny, G.D., Galinsky, I., Stone, R.M., Gray, N.S., D'Andrea, A.D., Parmar, K., Small-molecule inhibitors of USP1 target ID1 degradation in leukemic cells. Mol. Cancer Ther. 12:12 (2013), 2651–2662.
34. Mothi, M., Sampson, S., Pimozide for schizophrenia or related psychoses. Cochrane Database Syst. Rev., 2013, 11, 10.1002/14651858.CD001949 CD001949.
35. Munro, A., Mok, H., An overview of treatment in paranoia/delusional disorder. Can. J. Psychiatry 40:10 (1995), 616–622.
36. Neifeld, J.P., Tormey, D.C., Baker, M.A., Meyskens, F.L. Jr, Taub, R.N., Phase II trial of the dopaminergic inhibitor pimozide in previously treated melanoma patients. Cancer Treat. Rep. 67:2 (1983), 155–157.
37. Nelson, E.A., Walker, S.R., Weisberg, E., Bar-Natan, M., Barrett, R., Gashin, L.B., Terrell, S., Klitgaard, J.L., Santo, L., Addorio, M.R., Ebert, B.L., Griffin, J.D., Frank, D.A., The STAT5 inhibitor pimozide decreases survival of chronic myelogenous leukemia cells resistant to kinase inhibitors. Blood 117:12 (2011), 3421–3429.
38. Nelson, E.A., Walker, S.R., Xiang, M., Weisberg, E., Bar-Natan, M., Barrett, R., Liu, S., Kharbanda, S., Christie, A.L., Nicolais, M., Griffin, J.D., Stone, R.M., Kung, A.L., Frank, D.A., The STAT5 inhibitor pimozide displays efficacy in models of acute myelogenous leukemia driven by FLT3 mutations. Genes Cancer 3:7–8 (2012), 503–511.
39. Nogami, A., Oshikawa, G., Okada, K., Fukutake, S., Umezawa, Y., Nagao, T., Kurosu, T., Miura, O., FLT3-ITD confers resistance to the PI3K/Akt pathway inhibitors by protecting the mTOR/4EBP1/Mcl-1 pathway through STAT5 activation in acute myeloid leukemia. Oncotarget 6:11 (2015), 9189–9205.
40. Ohsawa, M., Murakami, T., Kume, K., Possible involvement of insulin resistance in the progression of cancer cachexia in mice. Yakugaku Zasshi 136:5 (2016), 687–692.
41. Oruch, R., Hodneland, E., Pryme, I.F., Holmsen, H., Psychotropic drugs interfere with the tight coupling of polyphosphoinositide cycle metabolites in human platelets: a result of receptor-independent drug intercalation in the plasma membrane?. Biochim. Biophys. Acta 1778:10 (2008), 2165–2176.
42. Pappu, A.S., Hauser, G., Alterations of phospholipid metabolism in rat cerebral cortex mince induced by cationic amphiphilic drugs. J. Neurochem. 37:4 (1981), 1006–1014.
43. Ruben, L., Rasmussen, H., Phenothiazines and related compounds disrupt mitochondrial energy production by a calmodulin-independent reaction. Biochim. Biophys. Acta 637:3 (1981), 415–422.
44. Ryskalin, L., Limanaqi, F., Biagioni, F., Frati, A., Esposito, V., Calierno, M.T., Lenzi, P., Fornai, F., The emerging role of m-TOR up-regulation in brain astrocytoma. Histol. Histopathol. 32:5 (2017), 413–431.
45. Sleeman, M., Willis, G.L., Brodie, G., Smith, G.C., Changes in food intake and stomach contents of tumor-bearing rats after treatment with dopamine antagonists. Nutr. Cancer. 12:1 (1989), 49–55.
46. Striessnig, J., Pinggera, A., Kaur, G., Bock, G., Tuluc, P., L-type Ca(2+) channels in heart and brain. Wiley Interdiscip. Rev. Membr. Transp. Signal. 3:2 (2014), 15–38.
47. Strobl, J.S., Kirkwood, K.L., Lantz, T.K., Lewine, M.A., Peterson, V.A., Worley, J.F. 3rd, Inhibition of human breast cancer cell proliferation in tissue culture by the neuroleptic agents pimozide and thioridazine. Cancer Res. 50:17 (1990), 5399–5405.
48. Strobl, J.S., Melkoumian, Z., Peterson, V.A., Hylton, H., The cell death response to gamma-radiation in MCF-7 cells is enhanced by a neuroleptic drug, pimozide. Breast Cancer Res. Treat. 51:1 (1998), 83–95.
49. Taub, R.N., Baker, M.A., Treatment of metastatic malignant melanoma with pimozide. Lancet, 1(8116), 1979, 605.
50. Termine, C., Selvini, C., Rossi, G., Balottin, U., Emerging treatment strategies in tourette syndrome: what's in the pipeline?. Int. Rev. Neurobiol. 112 (2013), 445–448.
51. Uebele, V.N., Nuss, C.E., Fox, S.V., Garson, S.L., Cristescu, R., Doran, S.M., Kraus, R.L., Santarelli, V.P., Li, Y., Barrow, J.C., Yang, Z.Q., Schlegel, K.A., Rittle, K.E., Reger, T.S., Bednar, R.A., Lemaire, W., Mullen, F.A., Ballard, J.E., Tang, C., Dai, G., McManus, O.B., Koblan, K.S., Renger, J.J., Positive allosteric interaction of structurally diverse T-type calcium channel antagonists. Cell. Biochem. Biophys. 55:2 (2009), 81–93.
52. Vilner, B.J., Bowen, W.D., Sigma receptor-active neuroleptics are cytotoxic to C6 glioma cells in culture. Eur. J. Pharmacol. 244:2 (1993), 199–201.
53. Wang, Y., Lin, H.Q., Law, W.K., Liang, W.C., Zhang, J.F., Hu, J.S., Ip, T.M., Waye, M.M., Wan, D.C., Pimozide, a novel fatty acid binding protein 4 inhibitor, promotes adipogenesis of 3T3-L1 cells by activating pparγ. ACS Chem. Neurosci. 6:2 (2015), 211–218.
54. Wiklund, E.D., Catts, V.S., Catts, S.V., Ng, T.F., Whitaker, N.J., Brown, A.J., Lutze-Mann, L.H., Cytotoxic effects of antipsychotic drugs implicate cholesterol homeostasis as a novel chemotherapeutic target. Int. J. Cancer 126:1 (2010), 28–40.
55. Yang, C., Hao, Z., Zhu, C., Guo, Q., Mu, D., Zhang, L., Interventions for tic disorders: an overview of systematic reviews and meta analyses. Neurosci. Biobehav. Rev. 63 (2016), 239–255.
56. Zemrak, W.R., Kenna, G.A., Association of antipsychotic and antidepressant drugs with Q-T interval prolongation. Am. J. Health Syst. Pharm. 65:11 (2008), 1029–1038.
57. Zhang, L., Yu, J., Pan, H., Hu, P., Hao, Y., Cai, W., Zhu, H., Yu AD, Xie X., Ma, D., Yuan, J., Small molecule regulators of autophagy identified by an image-based high-throughput screen. Proc. Natl. Acad. Sci. U. S. A. 104:48 (2007), 19023–19028.
58. Zhou, W., Chen, M.K., Yu HT, Zhong Z.H., Cai, N., Chen, G.Z., Zhang, P., Chen, J.J., The antipsychotic drug pimozide inhibits cell growth in prostate cancer through suppression of STAT3 activation. Int. J. Oncol. 48:1 (2016), 322–328.