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 Letters
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-1074 Online ISSN: 1792-1082
Journal Cover
March-2017 Volume 13 Issue 3

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
March-2017 Volume 13 Issue 3

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 Open Access

Thioridazine has potent antitumor effects on lung cancer stem‑like cells

  • Authors:
    • Jiani Shen
    • Buyun Ma
    • Xinmin Zhang
    • Xiaozhu Sun
    • Jiancui Han
    • Yigang Wang
    • Liang Chu
    • Haineng Xu
    • Yu Yang
  • View Affiliations / Copyright

    Affiliations: Xinyuan Institute of Medicine and Biotechnology, School of Life Sciences, Zhejiang Sci‑Tech University, Hangzhou, Zhejiang 310018, P.R. China, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Science, Shanghai 200031, P.R. China, Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Copyright: © Shen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1563-1568
    |
    Published online on: January 25, 2017
       https://doi.org/10.3892/ol.2017.5651
  • 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 (TDZ), originally an anti-psychotic drug, suppresses several types of cancer and has specificity for leukemia stem cells. The present study was performed to assess its effect on lung cancer stem‑like cells, as its effect remains unknown. TDZ was utilized to treat lung cancer stem‑like cells (A549 sphere cells) and its cytotoxic effect and mechanism were evaluated in vitro and in vivo. TDZ elicited cytotoxicity in A549 sphere cells and inhibited their proliferation in a dose‑dependent pattern. A549 sphere cells treated with TDZ showed nuclear fragmentation, increased G0/G1 phase distribution, positive Annexin V staining, and a change in the expression of caspase family and cell cycle‑associated proteins. These results suggest the induction of caspase‑dependent apoptosis and cell cycle arrest. In addition, TDZ treatment resulted in significant inhibitory effect on mice xenografts established by A549 sphere cells. TDZ repressed growth of lung cancer stem‑like cells in vitro and in vivo, indicating its potential application in targeting lung cancer stem‑like cells.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Siegel RL, Miller KD and Jemal A: Cancer Statistics, 2015. CA Cancer J Clin. 65:5–29. 2015. View Article : Google Scholar : PubMed/NCBI

2 

She J, Yang P, Hong Q and Bai C: Lung cancer in China: Challenges and interventions. Chest. 143:1117–1126. 2013. View Article : Google Scholar : PubMed/NCBI

3 

Chen Z, Fillmore CM, Hammerman PS, Kim CF and Wong KK: Non-small-cell lung cancers: A heterogeneous set of diseases. Nat Rev Cancer. 14:535–546. 2014. View Article : Google Scholar : PubMed/NCBI

4 

Lapidot T, Sirard C, Vormoor J, Murdoch B, Hoang T, Caceres-Cortes J, Minden M, Paterson B, Caligiuri MA and Dick JE: A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature. 367:645–648. 1994. View Article : Google Scholar : PubMed/NCBI

5 

Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ and Clarke MF: Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA. 100:3983–3988. 2003. View Article : Google Scholar : PubMed/NCBI

6 

Singh SK, Clarke ID, Terasaki M, Bonn VE, Hawkins C, Squire J and Dirks PB: Identification of a cancer stem cell in human brain tumors. Cancer Res. 63:5821–5828. 2003.PubMed/NCBI

7 

Ricci-Vitiani L, Lombardi DG, Pilozzi E, Biffoni M, Todaro M, Peschle C and De Maria R: Identification and expansion of human colon-cancer-initiating cells. Nature. 445:111–115. 2007. View Article : Google Scholar : PubMed/NCBI

8 

Eramo A, Lotti F, Sette G, Pilozzi E, Biffoni M, Di Virgilio A, Conticello C, Ruco L, Peschle C and De Maria R: Identification and expansion of the tumorigenic lung cancer stem cell population. Cell Death Differ. 15:504–514. 2008. View Article : Google Scholar : PubMed/NCBI

9 

Roudi R, Madjd Z, Korourian A, Mehrazma M, Molanae S, Sabet MN and Shariftabrizi A: Clinical significance of putative cancer stem cell marker CD44 in different histological subtypes of lung cancer. Cancer Biomark. 14:457–467. 2014. View Article : Google Scholar : PubMed/NCBI

10 

Liu CC, Lin JH, Hsu TW, Su K, Li AF, Hsu HS and Hung SC: IL-6 enriched lung cancer stem-like cell population by inhibition of cell cycle regulators via DNMT1 upregulation. Int J Cancer. 136:547–559. 2015.PubMed/NCBI

11 

Zhou BB, Zhang HY, Damelin M, Geles KG, Grindley JC and Dirks PB: Tumour-initiating cells: Challenges and opportunities for anticancer drug discovery. Nat Rev Drug Discovery. 8:806–823. 2009. View Article : Google Scholar : PubMed/NCBI

12 

Ohman R and Axelsson R: Relationship between prolactin response and antipsychotic effect of thioridazine in psychiatric-patients. Eur J Clin Pharmacol. 14:111–116. 1978. View Article : Google Scholar : PubMed/NCBI

13 

Realmuto GM, Erickson WD, Yellin AM, Hopwood JH and Greenberg LM: Clinical comparison of thiothixene and thioridazine in schizophrenic adolescents. Am J Psychiatry. 141:440–442. 1984. View Article : Google Scholar : PubMed/NCBI

14 

van Soolingen D, Hernandez-Pando R, Orozco H, Aguilar D, Magis-Escurra C, Amaral L, van Ingen J and Boeree MJ: The antipsychotic thioridazine shows promising therapeutic activity in a mouse model of multidrug-resistant tuberculosis. PLoS One. 5:e126402010. View Article : Google Scholar : PubMed/NCBI

15 

Thorsing M, Klitgaard JK, Atilano ML, Skov MN, Kolmos HJ, Filipe SR and Kallipolitis BH: Thioridazine induces major changes in global gene expression and cell wall composition in methicillin-resistant Staphylococcus aureus USA300. PLoS One. 8:e645182013. View Article : Google Scholar : PubMed/NCBI

16 

Nagel D, Spranger S, Vincendeau M, Grau M, Raffegerst S, Kloo B, Hlahla D, Neuenschwander M, von Kries J Peter, Hadian K, et al: Pharmacologic inhibition of MALT1 protease by phenothiazines as a therapeutic approach for the treatment of aggressive ABC-DLBCL. Cancer Cell. 22:825–837. 2012. View Article : Google Scholar : PubMed/NCBI

17 

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. Microvascular Res. 84:227–234. 2012. View Article : Google Scholar

18 

Park MS, Dong SM, Kim BR, Seo SH, Kang S, Lee EJ, Lee SH and Rho SB: Thioridazine inhibits angiogenesis and tumor growth by targeting the VEGFR-2/PI3K/mTOR pathway in ovarian cancer xenografts. Oncotarget. 5:4929–4934. 2014. View Article : Google Scholar : PubMed/NCBI

19 

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

20 

Csonka A, Spengler G, Martins A, Ocsovszki I, Christensen JB, Hendricks O, Kristiansen JE, Amaral L and Molnar J: Effect of thioridazine stereoisomers on the drug accumulation of mouse lymphoma and human prostate cancer cell lines in vitro. In vivo. 27:815–820. 2013.PubMed/NCBI

21 

Mu J, Xu H, Yang Y, Huang W, Xiao J, Li M, Tan Z, Ding Q, Zhang L, Lu J, et al: Thioridazine, an antipsychotic drug, elicits potent antitumor effects in gastric cancer. Oncol Rep. 31:2107–2114. 2014.PubMed/NCBI

22 

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

23 

Sudo M, Mori S, Madan V, Yang H, Leong G and Koeffler HP: Short-hairpin RNA library: Identification of therapeutic partners for gefitinib-resistant non-small cell lung cancer. Oncotarget. 6:814–824. 2015. View Article : Google Scholar : PubMed/NCBI

24 

Sachlos E, Risueño Ruth M, Laronde S, Shapovalova Z, Lee JH, Russell J, Malig M, McNicol JD, Fiebig-Comyn A, Graham M, 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

25 

Ke XY, Lin Ng VW, Gao SJ, Tong YW, Hedrick JL and Yang YY: Co-delivery of thioridazine and doxorubicin using polymeric micelles for targeting both cancer cells and cancer stem cells. Biomaterials. 35:1096–1108. 2014. View Article : Google Scholar : PubMed/NCBI

26 

Yang Y, Xu HN, Huang WD, Ding M, Xiao J, Yang D, Li H, Liu XY and Chu L: Targeting lung cancer stem-like cells with TRAIL gene armed oncolytic adenovirus. J Cell Mol Med. 19:915–923. 2015. View Article : Google Scholar : PubMed/NCBI

27 

Korkaya H, Paulson A, Charafe-Jauffret E, Ginestier C, Brown M, Dutcher J, Clouthier SG and Wicha MS: Regulation of mammary stem/progenitor cells by PTEN/Akt/beta-catenin signaling. PLoS Biol. 7:e10001212009. View Article : Google Scholar : PubMed/NCBI

28 

Zhang XL, Jia Q, Lv L, Deng T and Gao J: Tumorspheres derived from HCC Cells are enriched with cancer stem cell-like cells and present high chemoresistance dependent on the Akt pathway. Anticancer Agents Med Chem. 15:755–763. 2015. View Article : Google Scholar : PubMed/NCBI

29 

Arguello PA and Gogos JA: A signaling pathway AKTing up in schizophrenia. J Clin Investig. 118:2018–2021. 2008.PubMed/NCBI

30 

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. View Article : Google Scholar : PubMed/NCBI

31 

Dongmei D, Xianlong F, Yu Y, Hongyan L, Qiang P and Haineng X: Inhibition of HeLa Cells by the combination of Thioridazine and Oncolytic Adenovirus ZD55-TRAIL and the exploration of its mechanism. Chinese J Cell Biol. 36:595–601. 2014.

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Shen J, Ma B, Zhang X, Sun X, Han J, Wang Y, Chu L, Xu H and Yang Y: Thioridazine has potent antitumor effects on lung cancer stem‑like cells. Oncol Lett 13: 1563-1568, 2017.
APA
Shen, J., Ma, B., Zhang, X., Sun, X., Han, J., Wang, Y. ... Yang, Y. (2017). Thioridazine has potent antitumor effects on lung cancer stem‑like cells. Oncology Letters, 13, 1563-1568. https://doi.org/10.3892/ol.2017.5651
MLA
Shen, J., Ma, B., Zhang, X., Sun, X., Han, J., Wang, Y., Chu, L., Xu, H., Yang, Y."Thioridazine has potent antitumor effects on lung cancer stem‑like cells". Oncology Letters 13.3 (2017): 1563-1568.
Chicago
Shen, J., Ma, B., Zhang, X., Sun, X., Han, J., Wang, Y., Chu, L., Xu, H., Yang, Y."Thioridazine has potent antitumor effects on lung cancer stem‑like cells". Oncology Letters 13, no. 3 (2017): 1563-1568. https://doi.org/10.3892/ol.2017.5651
Copy and paste a formatted citation
x
Spandidos Publications style
Shen J, Ma B, Zhang X, Sun X, Han J, Wang Y, Chu L, Xu H and Yang Y: Thioridazine has potent antitumor effects on lung cancer stem‑like cells. Oncol Lett 13: 1563-1568, 2017.
APA
Shen, J., Ma, B., Zhang, X., Sun, X., Han, J., Wang, Y. ... Yang, Y. (2017). Thioridazine has potent antitumor effects on lung cancer stem‑like cells. Oncology Letters, 13, 1563-1568. https://doi.org/10.3892/ol.2017.5651
MLA
Shen, J., Ma, B., Zhang, X., Sun, X., Han, J., Wang, Y., Chu, L., Xu, H., Yang, Y."Thioridazine has potent antitumor effects on lung cancer stem‑like cells". Oncology Letters 13.3 (2017): 1563-1568.
Chicago
Shen, J., Ma, B., Zhang, X., Sun, X., Han, J., Wang, Y., Chu, L., Xu, H., Yang, Y."Thioridazine has potent antitumor effects on lung cancer stem‑like cells". Oncology Letters 13, no. 3 (2017): 1563-1568. https://doi.org/10.3892/ol.2017.5651
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