Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1021-335X Online ISSN: 1791-2431
Journal Cover
May-2014 Volume 31 Issue 5

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
May-2014 Volume 31 Issue 5

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

Thioridazine, an antipsychotic drug, elicits potent antitumor effects in gastric cancer

  • Authors:
    • Jiasheng Mu
    • Haineng Xu
    • Yu Yang
    • Weidan Huang
    • Jing Xiao
    • Maolan Li
    • Zhujun Tan
    • Qichen Ding
    • Lin Zhang
    • Jianhua Lu
    • Xiangsong Wu
    • Yingbin Liu
  • View Affiliations / Copyright

    Affiliations: Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University school of Medicine, Shanghai 200092, P.R. China, State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, P.R. China, College of Life Science, Henan Normal University, Xinxiang, Henan 453007, P.R. China
  • Pages: 2107-2114
    |
    Published online on: March 6, 2014
       https://doi.org/10.3892/or.2014.3068
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Thioridazine, an antipsychotic drug, has been reported to induce apoptosis in various types of cancer cells, with specificity on targeting cancer stem cells (CSCs). However, whether it elicits anticancer effects in gastric cancer has never been reported. In the present study, we examined the ability of thioridazine to induce cell death in the gastric cancer cell lines NCI-N87 and AGS, and detected its in vivo tumor inhibition capacity. Thioridazine elicited cytotoxic effects on NCI-N87 and AGS cells in a dose-dependent manner, and inhibited the colony formation abilitiy of the NCI-N87 and AGS cells. Thioridazine treatment induced nuclear fragmentation, increased the proportion of sub-G1 phase cells, and elevated the percentage of Annexin V-positive cells, suggesting the occurrence of apoptosis. Moreover, thioridazine induced gastric cancer cell apoptosis in a caspase-dependent manner, as shown by a decrease in the precursors of casapse-9, caspase-8 and caspase-3, and by the ability of the caspase inhibitor Z-VAD-FMK to reverse the cytotoxic effect of thioridazine. JC-1 staining further revealed that thioridazine induced gastric cancer cell apoptosis via the mitochondrial pathway. In addition, thioridazine pretreatment inhibited the growth of NCI-N87 cell-derived tumors. The present study demonstrated that the antipsychotic drug thioridazine possesses anti-gastric cancer ability through in vitro and in vivo experiments, suggesting thioridazine as a potential drug in gastric cancer therapy.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Parkin DM, Bray F, Ferlay J and Pisani P: Global cancer statistics, 2002. CA Cancer J Clin. 55:74–108. 2005. View Article : Google Scholar

2 

Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar

3 

Kang S, Dong SM, Kim BR, Park MS, Trink B, Byun HJ and Rho SB: Thioridazine induces apoptosis by targeting the PI3K/Akt/mTOR pathway in cervical and endometrial cancer cells. Apoptosis. 17:989–997. 2012. View Article : Google Scholar : PubMed/NCBI

4 

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

5 

Gil-Ad I, Shtaif B, Levkovitz Y, Dayag M, Zeldich E and Weizman A: Characterization of phenothiazine-induced apoptosis in neuroblastoma and glioma cell lines: clinical relevance and possible application for brain-derived tumors. J Mol Neurosci. 22:189–198. 2004. View Article : Google Scholar : PubMed/NCBI

6 

Zhelev Z, Ohba H, Bakalova R, Hadjimitova V, Ishikawa M, Shinohara Y and Baba Y: 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. 53:267–275. 2004. View Article : Google Scholar

7 

Rho SB, Kim BR and Kang S: A gene signature-based approach identifies thioridazine as an inhibitor of phosphatidylinositol-3′-kinase (PI3K)/AKT pathway in ovarian cancer cells. Gynecol Oncol. 120:121–127. 2011.PubMed/NCBI

8 

Byun HJ, Lee JH, Kim BR, Kang S, Dong SM, Park MS, Lee SH, Park SH and Rho SB: Anti-angiogenic effects of thioridazine involving the FAK-mTOR pathway. Microvasc Res. 84:227–234. 2012. View Article : Google Scholar : PubMed/NCBI

9 

Ramu A, Spanier R, Rahamimoff H and Fuks Z: Restoration of doxorubicin responsiveness in doxorubicin-resistant P388 murine leukaemia cells. Br J Cancer. 50:501–507. 1984. View Article : Google Scholar : PubMed/NCBI

10 

Akiyama S, Shiraishi N, Kuratomi Y, Nakagawa M and Kuwano M: Circumvention of multiple-drug resistance in human cancer cells by thioridazine, trifluoperazine, and chlorpromazine. J Natl Cancer Inst. 76:839–844. 1986.PubMed/NCBI

11 

Castaing M, Loiseau A and Cornish-Bowden A: Synergy between verapamil and other multidrug-resistance modulators in model membranes. J Biosci. 32:737–746. 2007. View Article : Google Scholar : PubMed/NCBI

12 

Kamiwatari M, Nagata Y, Kikuchi H, Yoshimura A, Sumizawa T, Shudo N, Sakoda R, Seto K and Akiyama S: Correlation between reversing of multidrug resistance and inhibiting of [3H]azidopine photolabeling of P-glycoprotein by newly synthesized dihydropyridine analogues in a human cell line. Cancer Res. 49:3190–3195. 1989.

13 

Spengler G, Molnar J, Viveiros M and Amaral L: Thioridazine induces apoptosis of multidrug-resistant mouse lymphoma cells transfected with the human ABCB1 and inhibits the expression of P-glycoprotein. Anticancer Res. 31:4201–4205. 2011.PubMed/NCBI

14 

Sachlos E, Risueno RM, Laronde S, et al: Identification of drugs including a dopamine receptor antagonist that selectively target cancer stem cells. Cell. 149:1284–1297. 2012. View Article : Google Scholar : PubMed/NCBI

15 

Gil-Ad I, Shtaif B, Levkovitz Y, Nordenberg J, Taler M, Korov I and Weizman A: Phenothiazines induce apoptosis in a B16 mouse melanoma cell line and attenuate in vivo melanoma tumor growth. Oncol Rep. 15:107–112. 2006.PubMed/NCBI

16 

Efferth T and Volm M: Reversal of doxorubicin-resistance in sarcoma 180 tumor cells by inhibition of different resistance mechanisms. Cancer Lett. 70:197–202. 1993. View Article : Google Scholar : PubMed/NCBI

17 

Sutton LP and Rushlow WJ: The dopamine D2 receptor regulates Akt and GSK-3 via Dvl-3. Int J Neuropsychopharmacol. 15:965–979. 2012. View Article : Google Scholar : PubMed/NCBI

18 

Dubrovska A, Kim S, Salamone RJ, Walker JR, Maira SM, Garcia-Echeverria C, Schultz PG and Reddy VA: The role of PTEN/Akt/PI3K signaling in the maintenance and viability of prostate cancer stem-like cell populations. Proc Natl Acad Sci USA. 106:268–273. 2009. View Article : Google Scholar : PubMed/NCBI

19 

Takaishi S, Okumura T, Tu S, Wang SS, Shibata W, Vigneshwaran R, Gordon SA, Shimada Y and Wang TC: Identification of gastric cancer stem cells using the cell surface marker CD44. Stem Cells. 27:1006–1020. 2009. View Article : Google Scholar : PubMed/NCBI

20 

Gabalec F, Beranek M, Netuka D, Masopust V, Nahlovsky J, Cesak T, Marek J and Cap J: Dopamine 2 receptor expression in various pathological types of clinically non-functioning pituitary adenomas. Pituitary. 15:222–226. 2012. View Article : Google Scholar : PubMed/NCBI

21 

Gatto F and Hofland LJ: The role of somatostatin and dopamine D2 receptors in endocrine tumors. Endocr Relat Cancer. 18:R233–R251. 2011. View Article : Google Scholar : PubMed/NCBI

22 

Xu HN, Huang WD, Cai Y, et al: HCCS1-armed, quadruple-regulated oncolytic adenovirus specific for liver cancer as a cancer targeting gene-viro-therapy strategy. Mol Cancer. 10:1332011. View Article : Google Scholar : PubMed/NCBI

23 

Ding M, Cao X, Xu HN, et al: Prostate cancer-specific and potent antitumor effect of a DD3-controlled oncolytic virus harboring the PTEN gene. PLoS One. 7:e351532012. View Article : Google Scholar : PubMed/NCBI

24 

Sheikhpour M, Ahangari G, Sadeghizadeh M and Deezagi A: A novel report of apoptosis in human lung carcinoma cells using selective agonist of D2-like dopamine receptors: a new approach for the treatment of human non-small cell lung cancer. Int J Immunopathol Pharmacol. 26:393–402. 2013.PubMed/NCBI

25 

Senogles SE: D2 dopamine receptor-mediated antiproliferation in a small cell lung cancer cell line, NCI-H69. Anticancer Drugs. 18:801–807. 2007. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Mu J, Xu H, Yang Y, Huang W, Xiao J, Li M, Tan Z, Ding Q, Zhang L, Lu J, Lu J, et al: Thioridazine, an antipsychotic drug, elicits potent antitumor effects in gastric cancer. Oncol Rep 31: 2107-2114, 2014.
APA
Mu, J., Xu, H., Yang, Y., Huang, W., Xiao, J., Li, M. ... Liu, Y. (2014). Thioridazine, an antipsychotic drug, elicits potent antitumor effects in gastric cancer. Oncology Reports, 31, 2107-2114. https://doi.org/10.3892/or.2014.3068
MLA
Mu, J., Xu, H., Yang, Y., Huang, W., Xiao, J., Li, M., Tan, Z., Ding, Q., Zhang, L., Lu, J., Wu, X., Liu, Y."Thioridazine, an antipsychotic drug, elicits potent antitumor effects in gastric cancer". Oncology Reports 31.5 (2014): 2107-2114.
Chicago
Mu, J., Xu, H., Yang, Y., Huang, W., Xiao, J., Li, M., Tan, Z., Ding, Q., Zhang, L., Lu, J., Wu, X., Liu, Y."Thioridazine, an antipsychotic drug, elicits potent antitumor effects in gastric cancer". Oncology Reports 31, no. 5 (2014): 2107-2114. https://doi.org/10.3892/or.2014.3068
Copy and paste a formatted citation
x
Spandidos Publications style
Mu J, Xu H, Yang Y, Huang W, Xiao J, Li M, Tan Z, Ding Q, Zhang L, Lu J, Lu J, et al: Thioridazine, an antipsychotic drug, elicits potent antitumor effects in gastric cancer. Oncol Rep 31: 2107-2114, 2014.
APA
Mu, J., Xu, H., Yang, Y., Huang, W., Xiao, J., Li, M. ... Liu, Y. (2014). Thioridazine, an antipsychotic drug, elicits potent antitumor effects in gastric cancer. Oncology Reports, 31, 2107-2114. https://doi.org/10.3892/or.2014.3068
MLA
Mu, J., Xu, H., Yang, Y., Huang, W., Xiao, J., Li, M., Tan, Z., Ding, Q., Zhang, L., Lu, J., Wu, X., Liu, Y."Thioridazine, an antipsychotic drug, elicits potent antitumor effects in gastric cancer". Oncology Reports 31.5 (2014): 2107-2114.
Chicago
Mu, J., Xu, H., Yang, Y., Huang, W., Xiao, J., Li, M., Tan, Z., Ding, Q., Zhang, L., Lu, J., Wu, X., Liu, Y."Thioridazine, an antipsychotic drug, elicits potent antitumor effects in gastric cancer". Oncology Reports 31, no. 5 (2014): 2107-2114. https://doi.org/10.3892/or.2014.3068
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team