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
March 2013 Volume 29 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 2013 Volume 29 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

Inhibition of lymphangiogenic factor VEGF-C expression and production by the histone deacetylase inhibitor suberoylanilide hydroxamic acid in breast cancer cells

  • Authors:
    • Hsueh-Tsen Cheng
    • Wen-Chun Hung
  • View Affiliations / Copyright

    Affiliations: Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung 804, Taiwan, R.O.C., National Institute of Cancer Research, National Health Research Institutes, Tainan 704, Taiwan, R.O.C.
  • Pages: 1238-1244
    |
    Published online on: December 14, 2012
       https://doi.org/10.3892/or.2012.2188
  • 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

Suberoylanilide hydroxamic acid (SAHA), a potent histone deacetylase (HDAC) inhibitor, has been shown to exert anticancer effects in various types of human cancer and is now used in the clinic for cancer treatment. In addition to cytostatic and cytotoxic activities, SAHA also represses angiogenesis to inhibit tumor growth. However, the effect of SAHA on tumor lymphangiogenesis, a step in which cancer cells produce pro-lymphangiogenic factors such as vascular endothelial growth factor-C (VEGF-C) to stimulate proliferation and migration of lymphatic endothelial cells, remains largely unclear. In this study, we investigated the expression of VEGF-C in breast cancer cell lines and found that VEGF-C was highly expressed in MDA-MB-231, MCF-7, MDA-MB-453 and BT-474 cells. SAHA inhibited VEGF-C expression in a dose-dependent manner in these cell lines. The secretion of VEGF-C into conditioned medium was also suppressed. We cloned human VEGF-C gene promoter and demonstrated that SAHA directly repressed promoter activity in MDA-MB-231 cells. Promoter deletion assay suggested that SAHA repressed VEGF-C via the -185/+38 region which contained several transcription factor binding sites. Notably, we found that SAHA reduced Sp1, but not Sp3 and NF-κB protein levels. Treatment with Sp1 inhibitor mithramycin A also inhibited VEGF-C expression in breast cancer cells. In addition, enforced expression of Sp1 partially rescued the inhibition of VEGF-C by SAHA. Collectively, our results suggest that SAHA inhibits VEGF-C expression in breast cancer cells via transcriptional repression and this drug may exert anti-lymphangiogenic activity in cancer treatment.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Sarkies P and Sale JE: Cellular epigenetic stability and cancer. Trends Genet. 28:118–127. 2012. View Article : Google Scholar : PubMed/NCBI

2 

Esteller M and Herman JG: Cancer as an epigenetic disease: DNA methylation and chromatin alterations in human tumours. J Pathol. 196:1–7. 2002. View Article : Google Scholar : PubMed/NCBI

3 

Kouzarides T: Chromatin modifications and their function. Cell. 128:693–705. 2007. View Article : Google Scholar : PubMed/NCBI

4 

Huang L and Pardee AB: Suberoylanilide hydroxamic acid as a potential therapeutic agent for human breast cancer treatment. Mol Med. 6:849–866. 2000.PubMed/NCBI

5 

Kim MS, Kwon HJ, Lee YM, et al: Histone deacetylases induce angiogenesis by negative regulation of tumor suppressor genes. Nat Med. 7:437–443. 2001. View Article : Google Scholar : PubMed/NCBI

6 

Butler LM, Agus DB, Scher HI, et al: Suberoylanilide hydroxamic acid, an inhibitor of histone deacetylase, suppresses the growth of prostate cancer cells in vitro and in vivo. Cancer Res. 60:5165–5170. 2000.PubMed/NCBI

7 

Marks P, Rifkind RA, Richon VM, Breslow R, Miller T and Kelly WK: Histone deacetylases and cancer: causes and therapies. Nat Rev Cancer. 1:194–202. 2001. View Article : Google Scholar : PubMed/NCBI

8 

Minucci S and Pelicci PG: Histone deacetylase inhibitors and the promise of epigenetic (and more) treatments for cancer. Nat Rev Cancer. 6:38–51. 2006. View Article : Google Scholar : PubMed/NCBI

9 

Marks PA and Breslow R: Dimethyl sulfoxide to vorinostat: Development of this histone deacetylase inhibitor as an anticancer drug. Nat Biotechnol. 25:84–90. 2007. View Article : Google Scholar : PubMed/NCBI

10 

Duvic M and Vu J: Vorinostat: a new oral histone deacetylase inhibitor approved for cutaneous T-cell lymphoma. Expert Opin Investig Drugs. 16:1111–1120. 2007. View Article : Google Scholar : PubMed/NCBI

11 

Peart MJ, Tainton KM, Ruefli AA, et al: Novel mechanisms of apoptosis induced by histone deacetylase inhibitors. Cancer Res. 63:4460–4471. 2003.PubMed/NCBI

12 

Shao Y, Gao Z, Marks PA and Jiang X: Apoptotic and autophagic cell death induced by histone deacetylase inhibitors. Proc Natl Acad Sci USA. 101:18030–18035. 2004. View Article : Google Scholar : PubMed/NCBI

13 

Gui CY, Ngo L, Xu WS, Richon VM and Marks PA: Histone deacetylase (HDAC) inhibitor activation of p21WAF1 involves changes in promoter-associated proteins, including HDAC1. Proc Natl Acad Sci USA. 101:1241–1246. 2004. View Article : Google Scholar : PubMed/NCBI

14 

Mitsiades CS, Mitsiades NS, McMullan CJ, et al: Transcriptional signature of histone deacetylase inhibition in multiple myeloma: Biological and clinical implications. Proc Natl Acad Sci USA. 101:540–545. 2004. View Article : Google Scholar : PubMed/NCBI

15 

Khan AN and Tomasi TB: Histone deacetylase regulation of immune gene expression in tumor cells. Immunol Res. 40:164–178. 2008. View Article : Google Scholar : PubMed/NCBI

16 

Ogbomo H, Michaelis M, Kreuter J, Doerr HW and Cinatl J Jr: Histone deacetylase inhibitors suppress natural killer cell cytolytic activity. FEBS Lett. 581:1317–1322. 2007. View Article : Google Scholar : PubMed/NCBI

17 

Deroanne CF, Bonjean K, Servotte S, et al: Histone deacetylases inhibitors as anti-angiogenic agents altering vascular endothelial growth factor signaling. Oncogene. 21:427–436. 2002. View Article : Google Scholar : PubMed/NCBI

18 

Alitalo K, Tammela T and Petrova TV: Lymphangiogenesis in development and human disease. Nature. 438:946–953. 2005. View Article : Google Scholar : PubMed/NCBI

19 

Mandriota SJ, Jussila L, Jeltsch M, et al: Vascular endothelial growth factor-C- mediated lymphangiogenesis promotes tumour metastasis. EMBO J. 20:672–682. 2001. View Article : Google Scholar : PubMed/NCBI

20 

Maula SM, Luukkaa M, Grenman R, Jackson D, Jalkanen S and Ristamaki R: Intratumoral lymphatics are essential for the metastatic spread and prognosis in squamous cell carcinomas of the head and neck region. Cancer Res. 63:1920–1926. 2003.

21 

Dadras SS, Paul T, Bertoncini J, et al: Tumor lymphangiogenesis: a novel prognostic indaicator for cutaneous melanoma metastasis and survival. Am J Pathol. 162:1951–1960. 2003. View Article : Google Scholar : PubMed/NCBI

22 

Valtola R, Salven P, Heikkila P, et al: VEGFR-3 and its ligand VEGF-C are associated with angiogenesis in breast cancer. Am J Pathol. 154:1381–1390. 1999. View Article : Google Scholar : PubMed/NCBI

23 

Wang CA, Jedlicka P, Patrick AN, et al: Six1 induces lymphangiogenesis and metastasis via upregulation of VEGF-C in mouse models of breast cancer. J Clin Invest. 122:1895–1906. 2012. View Article : Google Scholar : PubMed/NCBI

24 

Skobe M, Hawighorst T, Jackson DG, et al: Induction of tumor lymphangiogenesis by VEGF-C promotes breast cancer metastasis. Nat Med. 7:192–198. 2001. View Article : Google Scholar : PubMed/NCBI

25 

Flaherty KT: Sorafenib in renal cell carcinoma. Clin Cancer Res. 13:S747–S752. 2007. View Article : Google Scholar

26 

Hanrahan EO and Heymach JV: Vascular endothelial growth factor receptor tyrosine kinase inhibitors Vandetanib (ZD6474) and AZD2171 in lung cancer. Clin Cancer Res. 13:S4617–S4622. 2007. View Article : Google Scholar : PubMed/NCBI

27 

Jimenez X, Lu D, Brennan L, et al: A recombinant, fully human, bispecific antibody neutralizes the biological activities mediated by both vascular endothelial growth factor receptors 2 and 3. Mol Cancer Ther. 4:427–434. 2005.

28 

Roberts N, Kloos B, Cassella M, et al: Inhibition of VEGFR-3 activation with the antagonistic antibody more potently suppresses lymph node and distant metastases than inactivation of VEGFR-2. Cancer Res. 66:2650–2657. 2006. View Article : Google Scholar : PubMed/NCBI

29 

McDonald DM: New antibody to stop tumor angiogenesis and lymphatic spread by blocking receptor partnering. Cancer Cell. 18:541–543. 2010. View Article : Google Scholar : PubMed/NCBI

30 

Rinderknecht M, Villa A, Ballmer-Hofer K, Neri D and Detmar M: Phage-derived fully human monoclonal antibody fragments to human vascular endothelial growth factor-C block its interaction with VEGF receptor-2 and 3. PLoS One. 5:e119412010. View Article : Google Scholar

31 

Chilov D, Kukk E, Taira S, et al: Genomic organization of human and mouse genes for vascular endothelial growth factor C. J Biol Chem. 272:25176–25183. 1997. View Article : Google Scholar : PubMed/NCBI

32 

Li L and Davie JR: The role of Sp1 and Sp3 in normal and cancer cell biology. Ann Anat. 192:275–283. 2010. View Article : Google Scholar : PubMed/NCBI

33 

Wang L, Wei D, Huang S, et al: Transcription factor Sp1 expression is a significant predictor of survival in human gastric cancer. Clin Cancer Res. 9:6371–6380. 2003.PubMed/NCBI

34 

Safe S and Abdelrahim M: Sp transcription factor family and its role in cancer. Eur J Cancer. 41:2438–2448. 2005. View Article : Google Scholar : PubMed/NCBI

35 

Hung JJ, Wang YT and Chang WC: Sp1 deacetylation induced by phorbol ester recruits p300 to activate 12(S)-lipoxygenase gene transcription. Mol Cell Biol. 26:1770–1785. 2006. View Article : Google Scholar : PubMed/NCBI

36 

Wang SA, Chuang JY, Yeh SH, et al: Heat shock protein 90 is important for Sp1 stability during mitosis. J Mol Biol. 387:1106–1119. 2009. View Article : Google Scholar : PubMed/NCBI

37 

Li D, Marchenko ND and Moll UM: SAHA shows preferential cytotoxicity in mutant p53 cancer cells by destabilizing mutant p53 through inhibition of the HDAC6- Hsp90 chaperone axis. Cell Death Differ. 19:1268–1276. 2012.PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Cheng H and Hung W: Inhibition of lymphangiogenic factor VEGF-C expression and production by the histone deacetylase inhibitor suberoylanilide hydroxamic acid in breast cancer cells. Oncol Rep 29: 1238-1244, 2013.
APA
Cheng, H., & Hung, W. (2013). Inhibition of lymphangiogenic factor VEGF-C expression and production by the histone deacetylase inhibitor suberoylanilide hydroxamic acid in breast cancer cells. Oncology Reports, 29, 1238-1244. https://doi.org/10.3892/or.2012.2188
MLA
Cheng, H., Hung, W."Inhibition of lymphangiogenic factor VEGF-C expression and production by the histone deacetylase inhibitor suberoylanilide hydroxamic acid in breast cancer cells". Oncology Reports 29.3 (2013): 1238-1244.
Chicago
Cheng, H., Hung, W."Inhibition of lymphangiogenic factor VEGF-C expression and production by the histone deacetylase inhibitor suberoylanilide hydroxamic acid in breast cancer cells". Oncology Reports 29, no. 3 (2013): 1238-1244. https://doi.org/10.3892/or.2012.2188
Copy and paste a formatted citation
x
Spandidos Publications style
Cheng H and Hung W: Inhibition of lymphangiogenic factor VEGF-C expression and production by the histone deacetylase inhibitor suberoylanilide hydroxamic acid in breast cancer cells. Oncol Rep 29: 1238-1244, 2013.
APA
Cheng, H., & Hung, W. (2013). Inhibition of lymphangiogenic factor VEGF-C expression and production by the histone deacetylase inhibitor suberoylanilide hydroxamic acid in breast cancer cells. Oncology Reports, 29, 1238-1244. https://doi.org/10.3892/or.2012.2188
MLA
Cheng, H., Hung, W."Inhibition of lymphangiogenic factor VEGF-C expression and production by the histone deacetylase inhibitor suberoylanilide hydroxamic acid in breast cancer cells". Oncology Reports 29.3 (2013): 1238-1244.
Chicago
Cheng, H., Hung, W."Inhibition of lymphangiogenic factor VEGF-C expression and production by the histone deacetylase inhibitor suberoylanilide hydroxamic acid in breast cancer cells". Oncology Reports 29, no. 3 (2013): 1238-1244. https://doi.org/10.3892/or.2012.2188
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