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
November-2019 Volume 18 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-2019 Volume 18 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

  • Supplementary Files
    • Supplementary_Data.pdf
Article Open Access

Anticancer effect of XAV939 is observed by inhibiting lactose dehydrogenase A in a 3‑dimensional culture of colorectal cancer cells

  • Authors:
    • Dahee Kim
    • Byumseok Koh
    • Kwang Rok Kim
    • Ki Young Kim
    • Won Hoon Jung
    • Hi Youn Kim
    • Sungsub Kim
    • Sang Dal Rhee
  • View Affiliations / Copyright

    Affiliations: Therapeutics and Biotechnology Division, Korea Research Institute of Chemical Technology, Yuseong‑gu, Daejeon 34114, Republic of Korea, Graduate School of New Drug Discovery and Development, Chungnam National University, Yuseong‑gu, Daejeon 34134, Republic of Korea
    Copyright: © Kim et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 4858-4864
    |
    Published online on: September 5, 2019
       https://doi.org/10.3892/ol.2019.10813
  • 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

XAV939, a tankyrase inhibitor, exerts an anticancer effect in 3‑dimensional (3D) cultured SW480 cells, however this is not exhibited in 2‑dimensional (2D) cultured SW480 cells. In the current study, XAV939 induced a 3.7‑fold increase in cellular apoptosis in 3D culture but not in the 2D culture. However, no significant changes were indicated in cell cycle distribution in the 2D or 3D culture. Based on the observation that protein expression, which was associated with the glycolytic pathway, was increased in the 3D culture, the effect of XAV939 on the patterns of glycolytic protein expression was assessed. XAV939 was revealed to decrease lactose dehydrogenase A (LDHA) expression in 3D cultured SW480 cells, but only exerted a small effect in the 2D culture. The coadministration of XAV939 with the LDHA inhibitor FX11 decreased proliferation in 3D cultured SW480 cells compared with the single administration of FX11, while there was no additive effect in the 2D culture. The lactate assay also indicated that XAV939 decreased lactate secretion in the 3D cell culture but not in the 2D culture. These results suggest that XAV939 exerts an anticancer effect through inhibition of LDHA in the 3D culture.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Li VS, Ng SS, Boersema PJ, Low TY, Karthaus WR, Gerlach JP, Mohammed S, Heck AJ, Maurice MM, Mahmoudi T and Clevers H: Wnt signaling through inhibition of β-catenin degradation in an intact Axin1 complex. Cell. 149:1245–1256. 2012. View Article : Google Scholar : PubMed/NCBI

2 

Schatoff EM, Leach BI and Dow LE: Wnt Signaling and Colorectal Cancer. Curr Colorectal Cancer Rep. 13:101–110. 2017. View Article : Google Scholar : PubMed/NCBI

3 

Zhan T, Rindtorff N and Boutros M: Wnt signaling in cancer. Oncogene. 36:1461–1473. 2017. View Article : Google Scholar : PubMed/NCBI

4 

Wu X, Luo F, Li J, Zhong X and Liu K: Tankyrase 1 inhibitior XAV939 increases chemosensitivity in colon cancer cell lines via inhibition of the Wnt signaling pathway. Int J Oncol. 48:1333–1340. 2016. View Article : Google Scholar : PubMed/NCBI

5 

Huang SM, Mishina YM, Liu S, Cheung A, Stegmeier F, Michaud GA, Charlat O, Wiellette E, Zhang Y, Wiessner S, et al: Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling. Nature. 461:614–620. 2009. View Article : Google Scholar : PubMed/NCBI

6 

Liu J, Pan S, Hsieh MH, Ng N, Sun F, Wang T, Kasibhatla S, Schuller AG, Li AG, Cheng D, et al: Targeting Wnt-driven cancer through the inhibition of Porcupine by LGK974. Proc Natl Acad Sci USA. 110:20224–20229. 2013. View Article : Google Scholar : PubMed/NCBI

7 

Chen B, Dodge ME, Tang W, Lu J, Ma Z, Fan CW, Wei S, Hao W, Kilgore J, Williams NS, et al: Small molecule-mediated disruption of Wnt-dependent signaling in tissue regeneration and cancer. Nat Chem Biol. 5:100–107. 2009. View Article : Google Scholar : PubMed/NCBI

8 

Waaler J, Machon O, Tumova L, Dinh H, Korinek V, Wilson SR, Paulsen JE, Pedersen NM, Eide TJ, Machonova O, et al: A novel tankyrase inhibitor decreases canonical Wnt signaling in colon carcinoma cells and reduces tumor growth in conditional APC mutant mice. Cancer Res. 72:2822–2832. 2012. View Article : Google Scholar : PubMed/NCBI

9 

Lau T, Chan E, Callow M, Waaler J, Boggs J, Blake RA, Magnuson S, Sambrone A, Schutten M, Firestein R, et al: 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

10 

Morrone S, Cheng Z, Moon RT, Cong F and Xu W: Crystal structure of a Tankyrase-Axin complex and its implications for Axin turnover and Tankyrase substrate recruitment. Proc Natl Acad Sci USA. 109:1500–1505. 2012. View Article : Google Scholar : PubMed/NCBI

11 

Tanaka N, Mashima T, Mizutani A, Sato A, Aoyama A, Gong B, Yoshida H, Muramatsu Y, Nakata K, Matsuura M, et al: APC mutations as a potential biomarker for sensitivity to tankyrase inhibitors in colorectal cancer. Mol Cancer Ther. 16:752–762. 2017. View Article : Google Scholar : PubMed/NCBI

12 

Kim YE, Jeon HJ, Kim D, Lee SY, Kim KY, Hong J, Maeng PJ, Kim KR and Kang D: Quantitative proteomic analysis of 2D and 3D cultured colorectal cancer cells: Profiling of tankyrase inhibitor XAV939-induced proteome. Sci Rep. 8:132552018. View Article : Google Scholar : PubMed/NCBI

13 

Koh B, Jeon H, Kim D, Kang D and Kim KR: Effect of fibroblast co-culture on the proliferation, viability and drug response of colon cancer cells. Oncol Lett. 17:2409–2417. 2019.PubMed/NCBI

14 

Lunt SY and Vander Heiden MG: Aerobic glycolysis: meeting the metabolic requirements of cell proliferation. Annu Rev Cell Dev Biol. 27:441–464. 2011. View Article : Google Scholar : PubMed/NCBI

15 

Kuipers EJ, Grady WM, Lieberman D, Seufferlein T, Sung JJ, Boelens PG, van de Velde CJ and Watanabe T: Colorectal cancer. Nat Rev Dis Primers. 1:150652015. View Article : Google Scholar : PubMed/NCBI

16 

Hanahan D and Weinberg RA: Hallmarks of cancer: The next generation. Cell. 144:646–674. 2011. View Article : Google Scholar : PubMed/NCBI

17 

Ooi AT and Gomperts BN: Molecular Pathways: Targeting cellular energy metabolism in cancer via inhibition of SLC2A1 and LDHA. Clin Cancer Res. 21:2440–2444. 2015. View Article : Google Scholar : PubMed/NCBI

18 

Le A, Cooper CR, Gouw AM, Dinavahi R, Maitra A, Deck LM, Royer RE, Vander Jagt DL, Semenza GL and Dang CV: Inhibition of lactate dehydrogenase A induces oxidative stress and inhibits tumor progression. Proc Natl Acad Sci USA. 107:2037–2042. 2010. View Article : Google Scholar : PubMed/NCBI

19 

Boroughs LK and DeBerardinis RJ: Metabolic pathways promoting cancer cell survival and growth. Nat Cell Biol. 17:351–359. 2015. View Article : Google Scholar : PubMed/NCBI

20 

Guo W, Shen F, Xiao W, Chen J and Pan F: Wnt inhibitor XAV939 suppresses the viability of small cell lung cancer NCI-H446 cells and induces apoptosis. Oncol Lett. 14:6585–6591. 2017.PubMed/NCBI

21 

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. View Article : Google Scholar : PubMed/NCBI

22 

Pavlova NN and Thompson CB: The Emerging Hallmarks of Cancer Metabolism. Cell Metab. 23:27–47. 2016. View Article : Google Scholar : PubMed/NCBI

23 

Dang CV, Le A and Gao P: MYC-induced cancer cell energy metabolism and therapeutic opportunities. Clin Cancer Res. 15:6479–6483. 2009. View Article : Google Scholar : PubMed/NCBI

24 

Flores A, Sandoval-Gonzalez S, Takahashi R, Krall A, Sathe L, Wei L, Radu C, Joly JH, Graham NA, Christofk HR and Lowry WE: Increased lactate dehydrogenase activity is dispensable in squamous carcinoma cells of origin. Nat Commun. 10:912019. View Article : Google Scholar : PubMed/NCBI

25 

He TL, Zhang YJ, Jiang H, Li XH, Zhu H and Zheng KL: The c-Myc-LDHA axis positively regulates aerobic glycolysis and promotes tumor progression in pancreatic cancer. Med Oncol. 32:1872015. View Article : Google Scholar : PubMed/NCBI

26 

Pelicano H, Martin DS, Xu RH and Huang P: Glycolysis inhibition for anticancer treatment. Oncogene. 25:4633–4646. 2006. View Article : Google Scholar : PubMed/NCBI

27 

Ono M, Yin P, Navarro A, Moravek MB, Coon V JS, Druschitz SA, Gottardi CJ and Bulun SE: Inhibition of canonical WNT signaling attenuates human leiomyoma cell growth. Fertil Steril. 101:1441–1449. 2014. View Article : Google Scholar : PubMed/NCBI

28 

Esen E, Chen J, Karner CM, Okunade AL, Patterson BW and Long F: WNT-LRP5 signaling induces Warburg effect through mTORC2 activation during osteoblast differentiation. Cell Metab. 17:745–755. 2013. View Article : Google Scholar : PubMed/NCBI

29 

He TL, Zhang YJ, Jiang H, Li XH, Zhu H and Zheng KL: The c-Myc-LDHA axis positively regulates aerobic glycolysis and promotes tumor progression in pancreatic cancer. Med Oncol. 32:1872015. View Article : Google Scholar : PubMed/NCBI

30 

Pate KT, Stringari C, Sprowl-Tanio S, Wang K, TeSlaa T, Hoverter NP, McQuade MM, Garner C, Digman MA, Teitell MA, et al: Wnt signaling directs a metabolic program of glycolysis and angiogenesis in colon cancer. EMBO J. 33:1454–1473. 2014. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Kim D, Koh B, Kim KR, Kim KY, Jung WH, Kim HY, Kim S and Rhee SD: Anticancer effect of XAV939 is observed by inhibiting lactose dehydrogenase A in a 3‑dimensional culture of colorectal cancer cells. Oncol Lett 18: 4858-4864, 2019.
APA
Kim, D., Koh, B., Kim, K.R., Kim, K.Y., Jung, W.H., Kim, H.Y. ... Rhee, S.D. (2019). Anticancer effect of XAV939 is observed by inhibiting lactose dehydrogenase A in a 3‑dimensional culture of colorectal cancer cells. Oncology Letters, 18, 4858-4864. https://doi.org/10.3892/ol.2019.10813
MLA
Kim, D., Koh, B., Kim, K. R., Kim, K. Y., Jung, W. H., Kim, H. Y., Kim, S., Rhee, S. D."Anticancer effect of XAV939 is observed by inhibiting lactose dehydrogenase A in a 3‑dimensional culture of colorectal cancer cells". Oncology Letters 18.5 (2019): 4858-4864.
Chicago
Kim, D., Koh, B., Kim, K. R., Kim, K. Y., Jung, W. H., Kim, H. Y., Kim, S., Rhee, S. D."Anticancer effect of XAV939 is observed by inhibiting lactose dehydrogenase A in a 3‑dimensional culture of colorectal cancer cells". Oncology Letters 18, no. 5 (2019): 4858-4864. https://doi.org/10.3892/ol.2019.10813
Copy and paste a formatted citation
x
Spandidos Publications style
Kim D, Koh B, Kim KR, Kim KY, Jung WH, Kim HY, Kim S and Rhee SD: Anticancer effect of XAV939 is observed by inhibiting lactose dehydrogenase A in a 3‑dimensional culture of colorectal cancer cells. Oncol Lett 18: 4858-4864, 2019.
APA
Kim, D., Koh, B., Kim, K.R., Kim, K.Y., Jung, W.H., Kim, H.Y. ... Rhee, S.D. (2019). Anticancer effect of XAV939 is observed by inhibiting lactose dehydrogenase A in a 3‑dimensional culture of colorectal cancer cells. Oncology Letters, 18, 4858-4864. https://doi.org/10.3892/ol.2019.10813
MLA
Kim, D., Koh, B., Kim, K. R., Kim, K. Y., Jung, W. H., Kim, H. Y., Kim, S., Rhee, S. D."Anticancer effect of XAV939 is observed by inhibiting lactose dehydrogenase A in a 3‑dimensional culture of colorectal cancer cells". Oncology Letters 18.5 (2019): 4858-4864.
Chicago
Kim, D., Koh, B., Kim, K. R., Kim, K. Y., Jung, W. H., Kim, H. Y., Kim, S., Rhee, S. D."Anticancer effect of XAV939 is observed by inhibiting lactose dehydrogenase A in a 3‑dimensional culture of colorectal cancer cells". Oncology Letters 18, no. 5 (2019): 4858-4864. https://doi.org/10.3892/ol.2019.10813
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