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
International Journal of Oncology
Join Editorial Board Propose a Special Issue
Print ISSN: 1019-6439 Online ISSN: 1791-2423
Journal Cover
May-2015 Volume 46 Issue 5

Full Size Image

Cover Legend PDF

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-2015 Volume 46 Issue 5

Full Size Image

Cover Legend PDF

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

Sodium valproate, a histone deacetylase inhibitor, modulates the vascular endothelial growth inhibitor-mediated cell death in human osteosarcoma and vascular endothelial cells

  • Authors:
    • Koji Yamanegi
    • Mutsuki Kawabe
    • Hiroyuki Futani
    • Hiroshi Nishiura
    • Naoko Yamada
    • Nahoko Kato-Kogoe
    • Hiromitsu Kishimoto
    • Shinichi Yoshiya
    • Keiji Nakasho
  • View Affiliations / Copyright

    Affiliations: Department of Pathology, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan, Department of Orthopedic Surgery, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan, Department of Oral and Maxillofacial Surgery, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan
  • Pages: 1994-2002
    |
    Published online on: March 12, 2015
       https://doi.org/10.3892/ijo.2015.2924
  • 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

The level of vascular endothelial growth inhibitor (VEGI) has been reported to be negatively associated with neovascularization in malignant tumors. The soluble form of VEGI is a potent anti-angiogenic factor due to its effects in inhibiting endothelial cell proliferation. This inhibition is mediated by death receptor 3 (DR3), which contains a death domain in its cytoplasmic tail capable of inducing apoptosis that can be subsequently blocked by decoy receptor 3 (DcR3). We investigated the effects of sodium valproate (VPA) and trichostatin A (TSA), histone deacetylase inhibitors, on the expression of VEGI and its related receptors in human osteosarcoma (OS) cell lines and human microvascular endothelial (HMVE) cells. Consequently, treatment with VPA and TSA increased the VEGI and DR3 expression levels without inducing DcR3 production in the OS cell lines. In contrast, the effect on the HMVE cells was limited, with no evidence of growth inhibition or an increase in the DR3 and DcR3 expression. However, VPA-induced soluble VEGI in the OS cell culture medium markedly inhibited the vascular tube formation of HMVE cells, while VEGI overexpression resulted in enhanced OS cell death. Taken together, the HDAC inhibitor has anti-angiogenesis and antitumor activities that mediate soluble VEGI/DR3-induced apoptosis via both autocrine and paracrine pathways. This study indicates that the HDAC inhibitor may be exploited as a therapeutic strategy modulating the soluble VEGI/DR3 pathway in osteosarcoma patients.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Messerschmitt PJ, Garcia RM, Abdul-Karim FW, Greenfield EM and Getty PJ: Osteosarcoma. J Am Acad Orthop Surg. 17:515–527. 2009.PubMed/NCBI

2 

Shen H and Laird PW: Interplay between the cancer genome and epigenome. Cell. 153:38–55. 2013. View Article : Google Scholar : PubMed/NCBI

3 

Kristensen LS, Nielsen HM and Hansen LL: Epigenetics and cancer treatment. Eur J Pharmacol. 625:131–142. 2009. View Article : Google Scholar : PubMed/NCBI

4 

Ferguson LR, Tatham AL, Lin Z and Denny WA: Epigenetic regulation of gene expression as an anticancer drug target. Curr Cancer Drug Targets. 11:199–212. 2011. View Article : Google Scholar

5 

Rogawski MA and Löscher W: The neurobiology of antiepileptic drugs. Nat Rev Neurosci. 5:553–564. 2004. View Article : Google Scholar : PubMed/NCBI

6 

Bialer M: Why are antiepileptic drugs used for nonepileptic conditions? Epilepsia. 53(Suppl 7): S26–S33. 2012. View Article : Google Scholar

7 

Dickinson M, Johnstone RW and Prince HM: Histone deacetylase inhibitors: Potential targets responsible for their anticancer effect. Invest New Drugs. 28(Suppl 1): S3–S20. 2010. View Article : Google Scholar

8 

Tan KB, Harrop J, Reddy M, Young P, Terrett J, Emery J, Moore G and Truneh A: Characterization of a novel TNF-like ligand and recently described TNF ligand and TNF receptor superfamily genes and their constitutive and inducible expression in hematopoietic and non-hematopoietic cells. Gene. 204:35–46. 1997. View Article : Google Scholar

9 

Zhai Y, Ni J, Jiang GW, et al: VEGI, a novel cytokine of the tumor necrosis factor family, is an angiogenesis inhibitor that suppresses the growth of colon carcinomas in vivo. FASEB J. 13:181–189. 1999.PubMed/NCBI

10 

Parr C, Gan CH, Watkins G and Jiang WG: Reduced vascular endothelial growth inhibitor (VEGI) expression is associated with poor prognosis in breast cancer patients. Angiogenesis. 9:73–81. 2006. View Article : Google Scholar : PubMed/NCBI

11 

Chew LJ, Pan H, Yu J, Tian S, Huang WQ, Zhang JY, Pang S and Li LY: A novel secreted splice variant of vascular endothelial cell growth inhibitor. FASEB J. 16:742–744. 2002.PubMed/NCBI

12 

Migone TS, Zhang J, Luo X, Zhuang L, Chen C, Hu B, Hong JS, Perry JW, Chen S-F and Zhou JXH: TL1A is a TNF-like ligand for DR3 and TR6/DcR3 and functions as a T cell costimulator. Immunity. 16:479–492. 2002. View Article : Google Scholar : PubMed/NCBI

13 

Grimaldo S, Tian F and Li LY: Sensitization of endothelial cells to VEGI-induced apoptosis by inhibiting the NF-kappaB pathway. Apoptosis. 14:788–795. 2009. View Article : Google Scholar : PubMed/NCBI

14 

Ge Z, Sanders AJ, Ye L and Jiang WG: Aberrant expression and function of death receptor-3 and death decoy receptor-3 in human cancer. Exp Ther Med. 2:167–172. 2011.PubMed/NCBI

15 

Liang PH, Tian F, Lu Y, Duan B, Stolz DB and Li LY: Vascular endothelial growth inhibitor (VEGI; TNFSF15) inhibits bone marrow-derived endothelial progenitor cell incorporation into Lewis lung carcinoma tumors. Angiogenesis. 14:61–68. 2011. View Article : Google Scholar :

16 

Chinnaiyan AM, O’Rourke K, Yu GL, Lyons RH, Garg M, Duan DR, Xing L, Gentz R, Ni J and Dixit VM: Signal transduction by DR3, a death domain-containing receptor related to TNFR-1 and CD95. Science. 274:990–992. 1996. View Article : Google Scholar : PubMed/NCBI

17 

Yang CR, Hsieh SL, Teng CM, Ho FM, Su WL and Lin WW: Soluble decoy receptor 3 induces angiogenesis by neutralization of TL1A, a cytokine belonging to tumor necrosis factor superfamily and exhibiting angiostatic action. Cancer Res. 64:1122–1129. 2004. View Article : Google Scholar : PubMed/NCBI

18 

Hou W, Medynski D, Wu S, Lin X and Li LY: VEGI-192, a new isoform of TNFSF15, specifically eliminates tumor vascular endothelial cells and suppresses tumor growth. Clin Cancer Res. 11:5595–5602. 2005. View Article : Google Scholar : PubMed/NCBI

19 

Zhang Z and Li LY: TNFSF15 modulates neovascularization and inflammation. Cancer Microenviron. 5:237–247. 2012. View Article : Google Scholar : PubMed/NCBI

20 

Xiao Q, Hsu CY, Chen H, Ma X, Xu J and Lee JM: Characterization of cis-regulatory elements of the vascular endothelial growth inhibitor gene promoter. Biochem J. 388:913–920. 2005. View Article : Google Scholar : PubMed/NCBI

21 

Marks PA and Xu WS: Histone deacetylase inhibitors: Potential in cancer therapy. J Cell Biochem. 107:600–608. 2009. View Article : Google Scholar : PubMed/NCBI

22 

Bai C, Connolly B, Metzker ML, et al: Overexpression of M68/DcR3 in human gastrointestinal tract tumors independent of gene amplification and its location in a four-gene cluster. Proc Natl Acad Sci USA. 97:1230–1235. 2000. View Article : Google Scholar : PubMed/NCBI

23 

Takahama Y, Yamada Y, Emoto K, Fujimoto H, Takayama T, Ueno M, Uchida H, Hirao S, Mizuno T and Nakajima Y: The prognostic significance of overexpression of the decoy receptor for Fas ligand (DcR3) in patients with gastric carcinomas. Gastric Cancer. 5:61–68. 2002. View Article : Google Scholar : PubMed/NCBI

24 

Ge Z, Sanders AJ, Ye L, Wang Y and Jiang WG: Expression of death decoy receptor-3 (DcR3) in human breast cancer and its functional effects on breast cancer cells in vitro. J Exp Ther Oncol. 9:109–118. 2011.PubMed/NCBI

25 

Zong L, Chen P and Wang DX: Death decoy receptor overexpression and increased malignancy risk in colorectal cancer. World J Gastroenterol. 20:4440–4445. 2014. View Article : Google Scholar : PubMed/NCBI

26 

Qian DZ, Kachhap SK, Collis SJ, Verheul HM, Carducci MA, Atadja P and Pili R: Class II histone deacetylases are associated with VHL-independent regulation of hypoxia-inducible factor 1 alpha. Cancer Res. 66:8814–8821. 2006. View Article : Google Scholar : PubMed/NCBI

27 

Kong X, Lin Z, Liang D, Fath D, Sang N and Caro J: Histone deacetylase inhibitors induce VHL and ubiquitin-independent proteasomal degradation of hypoxia-inducible factor 1alpha. Mol Cell Biol. 26:2019–2028. 2006. View Article : Google Scholar : PubMed/NCBI

28 

Kang FW, Que L, Wu M, Wang ZL and Sun J: Effects of trichostatin A on HIF-1α and VEGF expression in human tongue squamous cell carcinoma cells in vitro. Oncol Rep. 28:193–199. 2012.PubMed/NCBI

29 

Zhao Y, Yu D, Wu H, Liu H, Zhou H, Gu R, Zhang R, Zhang S and Wu G: Anticancer activity of SAHA, a potent histone deacetylase inhibitor, in NCI-H460 human large-cell lung carcinoma cells in vitro and in vivo. Int J Oncol. 44:451–458. 2014.

30 

Xiao T, Fan JK, Huang HL, Gu JF, Li LY and Liu XY: VEGI-armed oncolytic adenovirus inhibits tumor neovascularization and directly induces mitochondria-mediated cancer cell apoptosis. Cell Res. 20:367–378. 2010. View Article : Google Scholar

31 

Mück C, Herndler-Brandstetter D, Micutkova L, Grubeck-Loebenstein B and Jansen-Dürr P: Two functionally distinct isoforms of TL1A (TNFSF15) generated by differential ectodomain shedding. J Gerontol A Biol Sci Med Sci. 65:1165–1180. 2010. View Article : Google Scholar : PubMed/NCBI

32 

Yamanegi K, Yamane J, Kobayashi K, et al: Downregulation of matrix metalloproteinase-9 mRNA by valproic acid plays a role in inhibiting the shedding of MHC class I-related molecules A and B on the surface of human osteosarcoma cells. Oncol Rep. 28:1585–1590. 2012.PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Yamanegi K, Kawabe M, Futani H, Nishiura H, Yamada N, Kato-Kogoe N, Kishimoto H, Yoshiya S and Nakasho K: Sodium valproate, a histone deacetylase inhibitor, modulates the vascular endothelial growth inhibitor-mediated cell death in human osteosarcoma and vascular endothelial cells. Int J Oncol 46: 1994-2002, 2015.
APA
Yamanegi, K., Kawabe, M., Futani, H., Nishiura, H., Yamada, N., Kato-Kogoe, N. ... Nakasho, K. (2015). Sodium valproate, a histone deacetylase inhibitor, modulates the vascular endothelial growth inhibitor-mediated cell death in human osteosarcoma and vascular endothelial cells. International Journal of Oncology, 46, 1994-2002. https://doi.org/10.3892/ijo.2015.2924
MLA
Yamanegi, K., Kawabe, M., Futani, H., Nishiura, H., Yamada, N., Kato-Kogoe, N., Kishimoto, H., Yoshiya, S., Nakasho, K."Sodium valproate, a histone deacetylase inhibitor, modulates the vascular endothelial growth inhibitor-mediated cell death in human osteosarcoma and vascular endothelial cells". International Journal of Oncology 46.5 (2015): 1994-2002.
Chicago
Yamanegi, K., Kawabe, M., Futani, H., Nishiura, H., Yamada, N., Kato-Kogoe, N., Kishimoto, H., Yoshiya, S., Nakasho, K."Sodium valproate, a histone deacetylase inhibitor, modulates the vascular endothelial growth inhibitor-mediated cell death in human osteosarcoma and vascular endothelial cells". International Journal of Oncology 46, no. 5 (2015): 1994-2002. https://doi.org/10.3892/ijo.2015.2924
Copy and paste a formatted citation
x
Spandidos Publications style
Yamanegi K, Kawabe M, Futani H, Nishiura H, Yamada N, Kato-Kogoe N, Kishimoto H, Yoshiya S and Nakasho K: Sodium valproate, a histone deacetylase inhibitor, modulates the vascular endothelial growth inhibitor-mediated cell death in human osteosarcoma and vascular endothelial cells. Int J Oncol 46: 1994-2002, 2015.
APA
Yamanegi, K., Kawabe, M., Futani, H., Nishiura, H., Yamada, N., Kato-Kogoe, N. ... Nakasho, K. (2015). Sodium valproate, a histone deacetylase inhibitor, modulates the vascular endothelial growth inhibitor-mediated cell death in human osteosarcoma and vascular endothelial cells. International Journal of Oncology, 46, 1994-2002. https://doi.org/10.3892/ijo.2015.2924
MLA
Yamanegi, K., Kawabe, M., Futani, H., Nishiura, H., Yamada, N., Kato-Kogoe, N., Kishimoto, H., Yoshiya, S., Nakasho, K."Sodium valproate, a histone deacetylase inhibitor, modulates the vascular endothelial growth inhibitor-mediated cell death in human osteosarcoma and vascular endothelial cells". International Journal of Oncology 46.5 (2015): 1994-2002.
Chicago
Yamanegi, K., Kawabe, M., Futani, H., Nishiura, H., Yamada, N., Kato-Kogoe, N., Kishimoto, H., Yoshiya, S., Nakasho, K."Sodium valproate, a histone deacetylase inhibitor, modulates the vascular endothelial growth inhibitor-mediated cell death in human osteosarcoma and vascular endothelial cells". International Journal of Oncology 46, no. 5 (2015): 1994-2002. https://doi.org/10.3892/ijo.2015.2924
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