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Antipsychotic agent pimozide promotes reversible proliferative suppression by inducing cellular quiescence in liver cancer

  • Authors:
    • Jia‑Jie Chen
    • Li‑Na Zhang
    • Nan Cai
    • Zhen Zhang
    • Kunmei Ji
  • View Affiliations / Copyright

    Affiliations: Department of Biochemistry and Molecular Biology, School of Medicine, Shenzhen University, Shenzhen, Guangdong 518060, P.R. China, College of Life Science and Oceanography, Shenzhen University, Shenzhen, Guangdong 518060, P.R. China
    Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1101-1109
    |
    Published online on: July 11, 2019
       https://doi.org/10.3892/or.2019.7229
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Abstract

The antipsychotic drug pimozide has been found to exhibit anticancer effects. Previously, it was demonstrated that pimozide inhibits hepatocellular carcinoma (HCC) cell growth, but its pharmacodynamic characteristics remain unclear. The aim of the present study was to investigate the reversibility and mechanism of the ability of pimozide to inhibit cell proliferation in liver cancer. Cell viability was determined by Cell Counting Kit‑8 and colony formation assay. The cell cycle distribution was analyzed by flow cytometry with Ki‑67 and PI staining. ROS production of HCC cells was detected with DCFH‑DA and inhibited with NAC treatment. Western blot assay was performed to detect the expression of related signaling molecules in HCC cells. Our results showed that pimozide promoted G0/G1 phase arrest in HCC cell lines without significant cell death. Its anti‑proliferative effects on HCC cells were reversible, consistent with involvement of cell quiescence and reactive oxygen species (ROS) production. Pimozide enhanced inhibition of HCC cell proliferation by sorafenib. In conclusion, elucidation of pimozide's reversible proliferation inhibition in liver cancer and additive activity with a well‑established anticancer drug warrants further exploration of the potential of pimozide as an adjuvant anticancer therapy.
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1 

Crissien AM and Frenette C: Current management of hepatocellular carcinoma. Gastroenterol Hepatol (N Y). 10:153–161. 2014.PubMed/NCBI

2 

Altekruse SF, McGlynn KA and Reichman ME: Hepatocellular carcinoma incidence, mortality, and survival trends in the united states from 1975 to 2005. J Clin Oncol. 27:1485–1491. 2009. View Article : Google Scholar : PubMed/NCBI

3 

Hoshida Y, Fuchs BC and Tanabe KK: Prevention of hepatocellular carcinoma: Potential targets, experimental models, and clinical challenges. Curr Can Drug Targets. 12:1129–1159. 2012. View Article : Google Scholar

4 

Cervello M, McCubrey JA, Cusimano A, Lampiasi N, Azzolina A and Montalto G: Targeted therapy for hepatocellular carcinoma: Novel agents on the horizon. Oncotarget. 3:236–260. 2012. View Article : Google Scholar : PubMed/NCBI

5 

Boguski MS, Mandl KD and Sukhatme VP: Drug discovery. Repurposing with a difference. Science. 324:1394–1395. 2009. View Article : Google Scholar : PubMed/NCBI

6 

Knapp S: New opportunities for kinase drug repurposing and target discovery. Br J Cancer. 118:936–937. 2018. View Article : Google Scholar : PubMed/NCBI

7 

Chen JJ, Cai N, Chen GZ, Jia CC, Qiu DB, Du C, Liu W, Yang Y, Long ZJ and Zhang Q: The neuroleptic drug pimozide inhibits stem-like cell maintenance and tumorigenicity in hepatocellular carcinoma. Oncotarget. 8:17593–17609. 2017.PubMed/NCBI

8 

Zhou W, Chen MK, Yu HT, Zhong ZH, Cai N, Chen GZ, Zhang P and Chen JJ: The antipsychotic drug pimozide inhibits cell growth in prostate cancer through suppression of STAT3 activation. Int J Oncol. 48:322–328. 2016. View Article : Google Scholar : PubMed/NCBI

9 

Cai N, Zhou W, Ye LL, Chen J, Liang QN, Chang G and Chen JJ: The STAT3 inhibitor pimozide impedes cell proliferation and induces ROS generation in human osteosarcoma by suppressing catalase expression. Am J Transl Res. 9:3853–3866. 2017.PubMed/NCBI

10 

Strobl JS, Melkoumian Z, Peterson VA and Hylton H: The cell death response to gamma-radiation in MCF-7 cells is enhanced by a neuroleptic drug, pimozide. Breast Cancer Res Treat. 51:83–95. 1998. View Article : Google Scholar : PubMed/NCBI

11 

Jia H, Ren W, Feng Y, Wei T, Guo M, Guo J, Zhao J, Song X, Wang M, Zhao T, et al: The enhanced antitumour response of pimozide combined with the IDO inhibitor L-MT in melanoma. Int J Oncol. 53:949–960. 2018.PubMed/NCBI

12 

Fako V, Yu Z, Henrich CJ, Ransom T, Budhu AS and Wang XW: Inhibition of wnt/β-catenin signaling in hepatocellular carcinoma by an antipsychotic drug pimozide. Int J Biol Sci. 12:768–775. 2016. View Article : Google Scholar : PubMed/NCBI

13 

Ren Y, Tao J, Jiang Z, Guo D and Tang J: Pimozide suppresses colorectal cancer via inhibition of Wnt/β-catenin signaling pathway. Life Sci. 209:267–273. 2018. View Article : Google Scholar : PubMed/NCBI

14 

Gonçalves JM, Silva CAB, Rivero ERC and Cordeiro MMR: Inhibition of cancer stem cells promoted by Pimozide. Clin Exp Pharmacol Physiol. 46:116–125. 2019. View Article : Google Scholar : PubMed/NCBI

15 

Yan D, Parker RE, Wang X, Frye SV, Earp HS III, DeRyckere D and Graham DK: MERTK promotes resistance to irreversible EGFR tyrosine kinase inhibitors in non-small cell lung cancers expressing wild-type EGFR family members. Clin Can Res. 24:6523–6535. 2018. View Article : Google Scholar

16 

Abdallah SM and Hirsh V: Irreversible tyrosine kinase inhibition of epidermal growth factor receptor with afatinib in EGFR activating mutation-positive advanced non-small-cell lung cancer. Curr Oncol. 25 (Suppl 1):S9–S17. 2018. View Article : Google Scholar : PubMed/NCBI

17 

Sagot I and Laporte D: Quiescence, an individual journey. Curr Genet. 65:695–699. 2019. View Article : Google Scholar : PubMed/NCBI

18 

Heldt FS, Barr AR, Cooper S, Bakal C and Novák B: A comprehensive model for the proliferation-quiescence decision in response to endogenous DNA damage in human cells. Proc Natl Acad Sci USA. 115:2532–2537. 2018. View Article : Google Scholar : PubMed/NCBI

19 

Cai N, Xie SJ, Qiu DB, Jia CC, Du C, Liu W, Chen JJ and Zhang Q: Potential effects of α-mangostin in the prevention and treatment of hepatocellular carcinoma. J Funct Foods. 26:309–318. 2016. View Article : Google Scholar

20 

Agarwal SM, Pal D, Gupta M and Saini R: Insight into discovery of next generation reversible TMLR inhibitors targeting EGFR activating and drug resistant T790M mutants. Curr Can Drug Targets. 17:617–636. 2017.

21 

Rybczynska M, Spitaler M, Knebel NG, Boeck G, Grunicke H and Hofmann J: Effects of miltefosine on various biochemical parameters in a panel of tumor cell lines with different sensitivities. Biochem Pharmacol. 62:765–772. 2001. View Article : Google Scholar : PubMed/NCBI

22 

Dakir EH, Pickard A, Srivastava K, McCrudden CM, Gross SR, Lloyd S, Zhang SD, Margariti A, Morgan R, Rudl PS and El-Tanani M: The anti-psychotic drug pimozide is a novel chemotherapeutic for breast cancer. Oncotarget. 9:34889–34910. 2018. View Article : Google Scholar : PubMed/NCBI

23 

Strobl JS, Kirkwood KL, Lantz TK, Lewine MA, Peterson VA and Worley JF III: Inhibition of human breast cancer cell proliferation in tissue culture by the neuroleptic agents pimozide and thioridazine. Cancer Res. 50:5399–5405. 1990.PubMed/NCBI

24 

Coller HA, Sang L and Roberts JM: A new description of cellular quiescence. PLoS Biol. 4:e832006. View Article : Google Scholar : PubMed/NCBI

25 

Aguirre-Ghiso JA: Models, mechanisms and clinical evidence for cancer dormancy. Nat Rev Cancer. 7:834–846. 2007. View Article : Google Scholar : PubMed/NCBI

26 

Alarcón T and Jensen HJ: Quiescence: A mechanism for escaping the effects of drug on cell populations. J R Soc Interface. 8:99–106. 2011. View Article : Google Scholar : PubMed/NCBI

27 

Fiore APZP, Ribeiro PF and Bruni-Cardoso A: Sleeping beauty and the microenvironment enchantment: Microenvironmental regulation of the proliferation-quiescence decision in normal tissues and in cancer development. Front Cell Dev Biol. 6:592018. View Article : Google Scholar : PubMed/NCBI

28 

Recasens A and Munoz L: Targeting cancer cell dormancy. Trends Pharmacol Sci. 40:30229–30233. 2019. View Article : Google Scholar

29 

Nelson EA, Walker SR, Xiang M, Weisberg E, Bar-Natan M, Barrett R, Liu S, Kharbanda S, Christie AL, Nicolais M, et al: The STAT5 inhibitor pimozide displays efficacy in models of acute myelogenous leukemia driven by FLT3 mutations. Genes Cancer. 3:503–511. 2012. View Article : Google Scholar : PubMed/NCBI

30 

Wishart DS, Feunang YD, Guo AC, Lo EJ, Marcu A, Grant JR, Sajed T, Johnson D, Li C, Sayeeda Z, et al: DrugBank 5.0: A major update to the DrugBank database for 2018. Nucleic Acids Res. 46(D1): D1074–D1082. 2018. View Article : Google Scholar : PubMed/NCBI

31 

Bhattarai D, Singh S, Jang Y, Hyeon Han S, Lee K and Choi Y: An insight into drug repositioning for the development of novel anti-cancer drugs. Curr Top Med Chem. 16:2156–2168. 2016. View Article : Google Scholar : PubMed/NCBI

32 

Samuel SM, Varghese E, Varghese S and Büsselberg D: Challenges and perspectives in the treatment of diabetes associated breast cancer. Cancer Treat Rev. 70:98–111. 2018. View Article : Google Scholar : PubMed/NCBI

33 

El-Arabey AA: Correction to: New insight for metformin against bladder cancer. Genes Environ. 40:162018. View Article : Google Scholar : PubMed/NCBI

34 

Forner A, Reig M and Bruix J: Hepatocellular carcinoma. Lancet. 391:1301–1314. 2018. View Article : Google Scholar : PubMed/NCBI

35 

Jiang C, Xu R, Li XX, Zhou YF, Xu XY, Yang Y, Wang HY and Zheng XFS: Sorafenib and carfilzomib synergistically inhibit the proliferation, survival, and metastasis of hepatocellular carcinoma. Mol Cancer Ther. 17:2610–2621. 2018. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Chen JJ, Zhang LN, Cai N, Zhang Z and Ji K: Antipsychotic agent pimozide promotes reversible proliferative suppression by inducing cellular quiescence in liver cancer. Oncol Rep 42: 1101-1109, 2019.
APA
Chen, J., Zhang, L., Cai, N., Zhang, Z., & Ji, K. (2019). Antipsychotic agent pimozide promotes reversible proliferative suppression by inducing cellular quiescence in liver cancer. Oncology Reports, 42, 1101-1109. https://doi.org/10.3892/or.2019.7229
MLA
Chen, J., Zhang, L., Cai, N., Zhang, Z., Ji, K."Antipsychotic agent pimozide promotes reversible proliferative suppression by inducing cellular quiescence in liver cancer". Oncology Reports 42.3 (2019): 1101-1109.
Chicago
Chen, J., Zhang, L., Cai, N., Zhang, Z., Ji, K."Antipsychotic agent pimozide promotes reversible proliferative suppression by inducing cellular quiescence in liver cancer". Oncology Reports 42, no. 3 (2019): 1101-1109. https://doi.org/10.3892/or.2019.7229
Copy and paste a formatted citation
x
Spandidos Publications style
Chen JJ, Zhang LN, Cai N, Zhang Z and Ji K: Antipsychotic agent pimozide promotes reversible proliferative suppression by inducing cellular quiescence in liver cancer. Oncol Rep 42: 1101-1109, 2019.
APA
Chen, J., Zhang, L., Cai, N., Zhang, Z., & Ji, K. (2019). Antipsychotic agent pimozide promotes reversible proliferative suppression by inducing cellular quiescence in liver cancer. Oncology Reports, 42, 1101-1109. https://doi.org/10.3892/or.2019.7229
MLA
Chen, J., Zhang, L., Cai, N., Zhang, Z., Ji, K."Antipsychotic agent pimozide promotes reversible proliferative suppression by inducing cellular quiescence in liver cancer". Oncology Reports 42.3 (2019): 1101-1109.
Chicago
Chen, J., Zhang, L., Cai, N., Zhang, Z., Ji, K."Antipsychotic agent pimozide promotes reversible proliferative suppression by inducing cellular quiescence in liver cancer". Oncology Reports 42, no. 3 (2019): 1101-1109. https://doi.org/10.3892/or.2019.7229
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