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
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
2014-February Volume 9 Issue 2

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
2014-February Volume 9 Issue 2

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

Valproic acid inhibits tumor angiogenesis in mice transplanted with Kasumi‑1 leukemia cells

  • Authors:
    • Zhi‑Hua Zhang
    • Chang‑Lai Hao
    • Peng Liu
    • Xia Tian
    • Li‑Hong Wang
    • Lei Zhao
    • Cui‑Min Zhu
  • View Affiliations / Copyright

    Affiliations: Affiliated Hospital of Chengde Medical College, Chengde, Hebei 067000, P.R. China, The First Hospital of Shijiazhuang City, Shijiazhuang, Hebei 050000, P.R. China, Chinese PLA 89 Hospital, Weifang, Shandong 261000, P.R. China
    Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 443-449
    |
    Published online on: November 28, 2013
       https://doi.org/10.3892/mmr.2013.1834
  • 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

Histone deacetylase (HDAC) inhibitors have been reported to inhibit tumor angiogenesis via the downregulation of angiogenic factors. Our previous in vitro studies demonstrated that valproic acid (VPA) exerted antitumor effects on Kasumi‑1 cells, which are human acute myeloid leukemia cells with an 8;21 chromosome translocation. In the present study, the effects of VPA on tumor angiogenesis were investigated in mice transplanted with Kasumi‑1 cells. Semi‑quantitative reverse transcription‑polymerase chain reaction, western blotting and immunohistochemistry were used to detect the expression of vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR2) and basic fibroblast growth factor (bFGF). The tumor microvessel density was measured following staining with an anti‑CD34 antibody. Chromatin immunoprecipitation was used to study the effect of VPA‑induced histone hyperacetylation on VEGF transcription. An intraperitoneal injection of VPA inhibited tumor growth and angiogenesis in mice transplanted with Kasumi‑1 cells. The mRNA and protein expression of VEGF, VEGFR2 and bFGF were inhibited by VPA treatment. In addition, VPA downregulated HDAC, increased histone H3 acetylation and enhanced the accumulation of hyperacetylated histone H3 on the VEGF promoters. The findings of the present study indicate that VPA, an HDAC inhibitor, exerts an antileukemic effect through an anti‑angiogenesis mechanism. In conclusion, the mechanism underlying VPA‑induced anti‑angiogenesis is associated with the suppression of angiogenic factors and their receptors. VPA may increase the accumulation of acetylated histones on the VEGF promoters, which possibly contributes to the regulation of angiogenic factors.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

View References

1 

Wichmann C, Chen L, Heinrich M, et al: Targeting the oligomerization domain of ETO interferes with RUNX1/ETO oncogenic activity in t(8;21)-positive leukemic cells. Cancer Res. 67:2280–2289. 2007. View Article : Google Scholar : PubMed/NCBI

2 

Minucci S, Nervi C, Lo Coco F and Pelicci PG: Histone deacetylases: a common molecular target for differentiation treatment of acute myeloid leukemias? Oncogene. 20:3110–3115. 2001. View Article : Google Scholar : PubMed/NCBI

3 

Gelmetti V, Zhang J, Fanelli M, Minucci S, Pelicci PG and Lazar MA: Aberrant recruitment of the nuclear receptor corepressor-histone deacetylase complex by the acute myeloid leukemia fusion partner ETO. Mol Cell Biol. 18:7185–7191. 1998.PubMed/NCBI

4 

Hug BA and Lazar MA: ETO interacting proteins. Oncogene. 23:4270–4274. 2004. View Article : Google Scholar : PubMed/NCBI

5 

Le XF, Claxton D, Kornblau S, Fan YH, Mu ZM and Chang KS: Characterization of the ETO and AML1-ETO proteins involved in 8;21 translocation in acute myelogenous leukemia. Eur J Haematol. 60:217–225. 1998.PubMed/NCBI

6 

Lutterbach B, Westendorf JJ, Linggi B, et al: ETO, a target of t(8;21) in acute leukemia, interacts with the N-CoR and mSin3 corepressors. Mol Cell Biol. 18:7176–7184. 1998.PubMed/NCBI

7 

Marks PA, Richon VM and Rifkind RA: Histone deacetylase inhibitors: inducers of differentiation or apoptosis of transformed cells. J Natl Cancer Inst. 92:1210–1216. 2000. View Article : Google Scholar : PubMed/NCBI

8 

Redner RL, Wang J and Liu JM: Chromatin remodeling and leukemia: new therapeutic paradigms. Blood. 94:417–428. 1999.PubMed/NCBI

9 

Hoeben A, Landuyt B, Highley MS, Wildiers H, Van Oosterom AT and De Bruijn EA: Vascular endothelial growth factor and angiogenesis. Pharmacol Rev. 56:549–580. 2004. View Article : Google Scholar : PubMed/NCBI

10 

Nussenbaum F and Herman IM: Tumor angiogenesis: insights and innovations. J Oncol. 2010:1326412010. View Article : Google Scholar : PubMed/NCBI

11 

Sasakawa Y, Naoe Y, Noto T, et al: Antitumor efficacy of FK228, a novel histone deacetylase inhibitor, depends on the effect on expression of angiogenesis factors. Biochem Pharmacol. 66:897–906. 2003. View Article : Google Scholar : PubMed/NCBI

12 

Göttlicher M, Minucci S, Zhu P, et al: Valproic acid defines a novel class of HDAC inhibitors inducing differentiation of transformed cells. EMBO J. 20:6969–6978. 2001.

13 

Zhao L, Zhang ZH and Zhu CM: Inhibitory effect of valproic acid on cell cycle of Kasumi-1 cell line and its mechanism. Zhonghua Xue Ye Xue Za Zhi. 29:802–805. 2008.(In Chinese).

14 

Zhu CM, Zhang ZH, Jiang FY, et al: Effects of histone deacetylase inhibitor on the expression of angiogenesis related factors in Kasumi-1 leukemic cell line. Zhonghua Xue Ye Xue Za Zhi. 31:466–469. 2010.(In Chinese).

15 

Poon RT, Ng IO, Lau C, et al: Tumor microvessel density as a predictor of recurrence after resection of hepatocellular carcinoma: a prospective study. J Clin Oncol. 20:1775–1785. 2002. View Article : Google Scholar : PubMed/NCBI

16 

Weidner N: Intratumor microvessel density as a prognostic factor in cancer. Am J Pathol. 147:9–19. 1995.PubMed/NCBI

17 

Larizza L, Magnani I and Beghini A: The Kasumi-1 cell line: a t(8;21)-kit mutant model for acute myeloid leukemia. Leuk Lymphoma. 46:247–255. 2005. View Article : Google Scholar : PubMed/NCBI

18 

Liu S, Klisovic RB, Vukosavljevic T, et al: Targeting AML1/ETO-histone deacetylase repressor complex: a novel mechanism for valproic acid-mediated gene expression and cellular differentiation in AML1/ETO-positive acute myeloid leukemia cells. J Pharmacol Exp Ther. 321:953–960. 2007. View Article : Google Scholar

19 

Hiramatsu A, Miwa H, Shikami M, et al: Disease-specific expression of VEGF and its receptors in AML cells: possible autocrine pathway of VEGF/type1 receptor of VEGF in t(15;17) AML and VEGF/type2 receptor of VEGF in t(8;21) AML. Leuk Lymphoma. 47:89–95. 2006. View Article : Google Scholar : PubMed/NCBI

20 

Imai N, Shikami M, Miwa H, et al: t(8;21) acute myeloid leukaemia cells are dependent on vascular endothelial growth factor (VEGF)/VEGF receptor type2 pathway and phosphorylation of Akt. Br J Haematol. 135:673–682. 2006. View Article : Google Scholar : PubMed/NCBI

21 

Mühlethaler-Mottet A, Meier R, Flahaut M, et al: Complex molecular mechanisms cooperate to mediate histone deacetylase inhibitors anti-tumour activity in neuroblastoma cells. Mol Cancer. 7:552008.

22 

Yang QC, Zeng BF, Shi ZM, et al: Inhibition of hypoxia-induced angiogenesis by trichostatin A via suppression of HIF-1a activity in human osteosarcoma. J Exp Clin Cancer Res. 25:593–599. 2006.PubMed/NCBI

23 

Mie Lee Y, Kim SH, Kim HS, et al: Inhibition of hypoxia-induced angiogenesis by FK228, a specific histone deacetylase inhibitor, via suppression of HIF-1alpha activity. Biochem Biophys Res Commun. 300:241–246. 2003.PubMed/NCBI

24 

Williams RJ: Trichostatin A, an inhibitor of histone deacetylase, inhibits hypoxia-induced angiogenesis. Expert Opin Investig Drugs. 10:1571–1573. 2001. View Article : Google Scholar : PubMed/NCBI

25 

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

26 

Tovar-Castillo LE, Cancino-Díaz JC, García-Vázquez F, et al: Under-expression of VHL and over-expression of HDAC-1, HIF-1alpha, LL-37, and IAP-2 in affected skin biopsies of patients with psoriasis. Int J Dermatol. 46:239–246. 2007. View Article : Google Scholar : PubMed/NCBI

27 

Ellis L, Hammers H and Pili R: Targeting tumor angiogenesis with histone deacetylase inhibitors. Cancer Lett. 280:145–153. 2009. View Article : Google Scholar : PubMed/NCBI

28 

Strahl BD and Allis CD: The language of covalent histone modifications. Nature. 403:41–45. 2000. View Article : Google Scholar : PubMed/NCBI

29 

Grunstein M: Histone acetylation in chromatin structure and transcription. Nature. 389:349–352. 1997. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Zhang ZH, Hao CL, Liu P, Tian X, Wang LH, Zhao L and Zhu CM: Valproic acid inhibits tumor angiogenesis in mice transplanted with Kasumi‑1 leukemia cells. Mol Med Rep 9: 443-449, 2014.
APA
Zhang, Z., Hao, C., Liu, P., Tian, X., Wang, L., Zhao, L., & Zhu, C. (2014). Valproic acid inhibits tumor angiogenesis in mice transplanted with Kasumi‑1 leukemia cells. Molecular Medicine Reports, 9, 443-449. https://doi.org/10.3892/mmr.2013.1834
MLA
Zhang, Z., Hao, C., Liu, P., Tian, X., Wang, L., Zhao, L., Zhu, C."Valproic acid inhibits tumor angiogenesis in mice transplanted with Kasumi‑1 leukemia cells". Molecular Medicine Reports 9.2 (2014): 443-449.
Chicago
Zhang, Z., Hao, C., Liu, P., Tian, X., Wang, L., Zhao, L., Zhu, C."Valproic acid inhibits tumor angiogenesis in mice transplanted with Kasumi‑1 leukemia cells". Molecular Medicine Reports 9, no. 2 (2014): 443-449. https://doi.org/10.3892/mmr.2013.1834
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang ZH, Hao CL, Liu P, Tian X, Wang LH, Zhao L and Zhu CM: Valproic acid inhibits tumor angiogenesis in mice transplanted with Kasumi‑1 leukemia cells. Mol Med Rep 9: 443-449, 2014.
APA
Zhang, Z., Hao, C., Liu, P., Tian, X., Wang, L., Zhao, L., & Zhu, C. (2014). Valproic acid inhibits tumor angiogenesis in mice transplanted with Kasumi‑1 leukemia cells. Molecular Medicine Reports, 9, 443-449. https://doi.org/10.3892/mmr.2013.1834
MLA
Zhang, Z., Hao, C., Liu, P., Tian, X., Wang, L., Zhao, L., Zhu, C."Valproic acid inhibits tumor angiogenesis in mice transplanted with Kasumi‑1 leukemia cells". Molecular Medicine Reports 9.2 (2014): 443-449.
Chicago
Zhang, Z., Hao, C., Liu, P., Tian, X., Wang, L., Zhao, L., Zhu, C."Valproic acid inhibits tumor angiogenesis in mice transplanted with Kasumi‑1 leukemia cells". Molecular Medicine Reports 9, no. 2 (2014): 443-449. https://doi.org/10.3892/mmr.2013.1834
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