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
November-2014 Volume 32 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
November-2014 Volume 32 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

XAV939 promotes apoptosis in a neuroblastoma cell line via telomere shortening

  • Authors:
    • Xiaohong Tian
    • Weijian Hou
    • Shuling Bai
    • Jun  Fan
    • Hao Tong
    • Yu Bai
  • View Affiliations / Copyright

    Affiliations: Department of Tissue Engineering, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning 110001, P.R. China, Department of Ophthalmology, The Second Hospital of Shijiazhuang, Shijiazhuang, Hebei 050051, P.R. China
  • Pages: 1999-2006
    |
    Published online on: September 2, 2014
       https://doi.org/10.3892/or.2014.3460
  • 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

Telomeres, telomerase and tankyrase (TNKS) have an extremely important and special association with human cell aging and cancer. Telomerase activity is abnormally high in cancer cells and is accompanied by the overexpression of tankyrase 1 (TNKS1). TNKS1 is a positive regulator of telomerase activation and telomere extension in the human body, indicating that TNKS1 may be a possible therapeutic target for cancer. XAV939 is a small-molecule inhibitor of TNKS1. The objective of the present study was to investigate the apoptotic effect of XAV939 on the neuroblastoma (NB) SH-SY5Y cell line, as well as the change in telomere length and telomerase activity and elucidate the mechanism from this perspective. In the present study, we initially treated SH-SY5Y cells with XAV939 and RNA interference (RNAi)-TNKS1, and subsequently chose the optimal sequence for RNAi-TNKS1. We then measured the telomere length using quantitative real-time polymerase chain reaction (qPCR) assay, detected the telomerase activity using the ELISA kit, observed apoptotic morphology by transmission electron microscopy, and detected the percentages of apoptotic cells using flow cytometry and Hoechst 33342 staining. We also determined the invasive ability by a cell invasion assay. The results showed that short hairpin RNA-2 (shRNA-2) was the optimal sequence for RNAi-TNKS1. Treatment with both XAV939 and RNAi-TNKS1 shortened the telomere length, promoted apoptosis and reduced the invasive ability of the SH-SY5Y cells, yet had no effect on telomerase activity. XAV939 promoted apoptosis and reduced the invasiveness of SH-SY5Y cells dependent on telomere shortening, and further research should be conducted to clarify the exact mechanisms. This research may contribute to the cure of malignant NB using multi-targeted therapy with small-molecule agents.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Ramirez R, Carracedo J, Jiménez R, et al: Massive telomere loss is an early event of DNA damage-induced apoptosis. J Biol Chem. 278:836–842. 2003. View Article : Google Scholar : PubMed/NCBI

2 

Lyons RJ, Deane R, Lynch DK, Ye ZS, Sanderson GM, Eyre HJ, Sutherland GR and Daly RJ: Identification of a novel human tankyrase through its interaction with the adaptor protein Grbl4. J Biol Chem. 276:17172–17180. 2001. View Article : Google Scholar : PubMed/NCBI

3 

De Rycker M, Venkatesan RN, Wei C and Price CM: Vertebrate tankyrase domain structure and sterile α motif (SAM)-mediated multimerization. Biochem J. 372:87–96. 2003.

4 

Seimiya H, Muramatsu Y, Smith S and Tsuruo T: Functional subdomain in the ankyrin domain of tankyrase 1 required for poly(ADP-ribosyl)ation of TRF1 and telomere elongation. Mol Cell Biol. 24:1944–1955. 2004. View Article : Google Scholar : PubMed/NCBI

5 

De Rycker M and Price CM: Tankyrase polymerization is controlled by its sterile α motif and poly(ADP-ribose) polymerase domains. Mol Cell Biol. 24:9802–9812. 2004.PubMed/NCBI

6 

Kaminker PG, Kim SH, Taylor RD, Zebarjadian Y, Funk WD, Morin GB, Yaswen P and Campisi J: TANK2, a new TRF1-associated poly(ADP-ribose) polymerase, causes rapid induction of cell death upon overexpression. J Biol Chem. 276:35891–35899. 2001. View Article : Google Scholar : PubMed/NCBI

7 

Seimiya H: The telomeric PARP, tankyrases, as targets for cancer therapy. Br J Cancer. 94:341–345. 2006. View Article : Google Scholar : PubMed/NCBI

8 

Smith S, Giriat I, Schmitt A and de Lange T: Tankyrase, a poly(ADP-ribose) polymerase at human telomeres. Science. 282:1484–1487. 1998. View Article : Google Scholar : PubMed/NCBI

9 

Hsiao SJ and Smith S: Sister telomeres rendered dysfunctional by persistent cohesion are fused by NHEJ. J Cell Biol. 184:515–526. 2009. View Article : Google Scholar : PubMed/NCBI

10 

Papeo G, Forte B, Orsini P, Perrera C, Posteri H, Scolaro A and Montagnoli A: Poly(ADP-ribose) polymerase inhibition in cancer therapy: are we close to maturity? Expert Opin Ther Pat. 19:1377–1400. 2009. View Article : Google Scholar : PubMed/NCBI

11 

Muramatsu Y, Ohishi T, Sakamoto M, Tsuruo T and Seimiya H: Cross-species difference in telomeric function of tankyrase 1. Cancer Sci. 98:850–857. 2007. View Article : Google Scholar : PubMed/NCBI

12 

Lu R, Pal J, Buon L, et al: Targeting homologous recombination and telomerase in Barrett’s adenocarcinoma: impact on telomere maintenance, genomic instability and tumor growth. Oncogene. 33:1495–1505. 2014.PubMed/NCBI

13 

Seimiya H, Muramatsu Y, Ohishi T and Tsuruo T: Tankyrase 1 as a target for telomere-directed molecular cancer therapeutics. Cancer Cell. 7:25–37. 2005. View Article : Google Scholar : PubMed/NCBI

14 

Tian XH, Hou WJ, Fang Y, Fan J, Tong H, Bai SL, Chen Q, Xu H and Li Y: XAV939, a tankyrase 1 inhibitior, promotes cell apoptosis in neuroblastoma cell lines by inhibiting Wnt/β-catenin signaling pathway. J Exp Clin Cancer Res. 32:1002013.PubMed/NCBI

15 

Huang SM, Mishina YM, Liu S, et al: Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling. Nature. 461:614–620. 2009. View Article : Google Scholar : PubMed/NCBI

16 

Dregalla RC, Zhou J, Idate RR, Battaglia CL, Liber HL and Bailey SM: Regulatory roles of tankyrase 1 at telomeres and in DNA repair: suppression of T-SCE and stabilization of DNA-PKcs. Aging. 2:691–708. 2010.PubMed/NCBI

17 

Sun J, Huang H and Zhu YY: Study on the expression of tankyrase in malignant hematopoietic cells and its relation with telomerase activity. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 12:11–15. 2004.(In Chinese).

18 

Cawthon RM: Telomere measurement by quantitative PCR. Nucleic Acids Res. 30:e472002. View Article : Google Scholar : PubMed/NCBI

19 

Cawthon RM: Telomere length measurement by a novel monochrome multiplex quantitative PCR method. Nucleic Acids Res. 37:e212009. View Article : Google Scholar : PubMed/NCBI

20 

Gelmini S, Poggesi M, Distante V, Bianchi S, Simi L, Luconi M, Raggi CC, Cataliotti L, Pazzagli M and Orlando C: Tankyrase, a positive regulator of telomere elongation, is overexpressed in human breast cancer. Cancer Lett. 216:81–87. 2004. View Article : Google Scholar : PubMed/NCBI

21 

Gelmini S, Quattrone S, Malentacchi F, Villari D, Travaglini F, Giannarini G, Della Melina A, Pazzagli M, Nicita G, Selli C and Orlando C: Tankyrase-1 mRNA expression in bladder cancer and paired urine sediment: preliminary experience. Clin Chem Lab Med. 45:862–866. 2007. View Article : Google Scholar : PubMed/NCBI

22 

Poonepalli A, Banerjee B, Ramnarayanan K, Palanisamy N, Putti TC and Hande MP: Telomere-mediated genomic instability and the clinico-pathological parameters in breast cancer. Genes Chromosomes Cancer. 47:1098–1109. 2008. View Article : Google Scholar : PubMed/NCBI

23 

Gelmini S, Poggesi M, Pinzani P, Mannurita SC, Cianchi F, Valanzano R and Orlando C: Distribution of Tankyrase-1 mRNA expression in colon cancer and its prospective correlation with progression stage. Oncol Rep. 16:1261–1266. 2006.PubMed/NCBI

24 

Shay JW and Bacchetti S: A survey of telomerase activity in human cancer. Eur J Cancer. 33:787–791. 1997. View Article : Google Scholar : PubMed/NCBI

25 

Andrews LG and Tollefsbol TO: Methods of telomerase inhibition. Methods Mol Biol. 405:1–8. 2007. View Article : Google Scholar : PubMed/NCBI

26 

Aubert G and Lansdorp PM: Telomeres and aging. Physiol Rev. 88:557–579. 2008. View Article : Google Scholar

27 

Baerlocher GM, Vulto I, de Jong G and Lansdorp PM: Flow cytometry and FISH to measure the average length of telomeres (flow FISH). Nat Protoc. 1:2365–2376. 2006. View Article : Google Scholar : PubMed/NCBI

28 

Poon SS and Lansdorp PM: Measurements of telomere length on individual chromosomes by image cytometry. Methods Cell Biol. 64:69–96. 2001. View Article : Google Scholar : PubMed/NCBI

29 

Zhang H, Yang MH, Zhao JJ, Chen L, Yu ST, Tang XD, Fang DC and Yang SM: Inhibition of tankyrase 1 in human gastric cancer cells enhances telomere shortening by telomerase inhibitors. Oncol Rep. 24:1059–1065. 2010.PubMed/NCBI

30 

Cerone MA, Burgess DJ, Naceur-Lombardelli C, Lord CJ and Ashworth A: High-throughput RNAi screening reveals novel regulators of telomerase. Cancer Res. 71:3328–3340. 2011. View Article : Google Scholar : PubMed/NCBI

31 

Bilsland AE, Hoare S, Stevenson K, et al: Dynamic telomerase gene suppression via network effects of GSK3 inhibition. PLoS One. 4:e64592009. View Article : Google Scholar : PubMed/NCBI

32 

Ohishi T, Tsuruo T and Seimiya H: Evaluation of tankyrase inhibition in whole cells. Methods Mol Biol. 405:133–146. 2007. View Article : Google Scholar : PubMed/NCBI

33 

Xu D, Li H and Liu JP: Inhibition of telomerase by targeting MAP kinase signaling. Methods Mol Biol. 405:147–165. 2007. View Article : Google Scholar : PubMed/NCBI

34 

Lau T, Chan E, Callow M, Waaler J, Boggs J, Blake RA, Magnuson S, Sambrone A, Schutten M, Firestein R, Machon O, Korinek V, Choo E, Diaz D, Merchant M, Polakis P, Holsworth DD, Krauss S and Costa M: A novel tankyrase small-molecule inhibitor suppresses APC mutation-driven colorectal tumor growth. Cancer Res. 73:3132–3144. 2013. View Article : Google Scholar : PubMed/NCBI

35 

Kim MK and Smith S: Persistent telomere cohesion triggers a prolonged anaphase. Mol Biol Cell. 25:30–40. 2014. View Article : Google Scholar : PubMed/NCBI

36 

Dynek JN and Smith S: Resolution of sister telomere association is required for progression through mitosis. Science. 304:97–100. 2004. View Article : Google Scholar : PubMed/NCBI

37 

Chang P, Coughlin M and Mitchison TJ: Tankyrase-1 polymerization of poly(ADP-ribose) is required for spindle structure and function. Nat Cell Biol. 7:1133–1139. 2005. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Tian X, Hou W, Bai S, Fan J, Tong H and Bai Y: XAV939 promotes apoptosis in a neuroblastoma cell line via telomere shortening. Oncol Rep 32: 1999-2006, 2014.
APA
Tian, X., Hou, W., Bai, S., Fan, J., Tong, H., & Bai, Y. (2014). XAV939 promotes apoptosis in a neuroblastoma cell line via telomere shortening. Oncology Reports, 32, 1999-2006. https://doi.org/10.3892/or.2014.3460
MLA
Tian, X., Hou, W., Bai, S., Fan, J., Tong, H., Bai, Y."XAV939 promotes apoptosis in a neuroblastoma cell line via telomere shortening". Oncology Reports 32.5 (2014): 1999-2006.
Chicago
Tian, X., Hou, W., Bai, S., Fan, J., Tong, H., Bai, Y."XAV939 promotes apoptosis in a neuroblastoma cell line via telomere shortening". Oncology Reports 32, no. 5 (2014): 1999-2006. https://doi.org/10.3892/or.2014.3460
Copy and paste a formatted citation
x
Spandidos Publications style
Tian X, Hou W, Bai S, Fan J, Tong H and Bai Y: XAV939 promotes apoptosis in a neuroblastoma cell line via telomere shortening. Oncol Rep 32: 1999-2006, 2014.
APA
Tian, X., Hou, W., Bai, S., Fan, J., Tong, H., & Bai, Y. (2014). XAV939 promotes apoptosis in a neuroblastoma cell line via telomere shortening. Oncology Reports, 32, 1999-2006. https://doi.org/10.3892/or.2014.3460
MLA
Tian, X., Hou, W., Bai, S., Fan, J., Tong, H., Bai, Y."XAV939 promotes apoptosis in a neuroblastoma cell line via telomere shortening". Oncology Reports 32.5 (2014): 1999-2006.
Chicago
Tian, X., Hou, W., Bai, S., Fan, J., Tong, H., Bai, Y."XAV939 promotes apoptosis in a neuroblastoma cell line via telomere shortening". Oncology Reports 32, no. 5 (2014): 1999-2006. https://doi.org/10.3892/or.2014.3460
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