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
September-2015 Volume 34 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
September-2015 Volume 34 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

Widdrol, a sesquiterpene isolated from Juniperus chinensis, inhibits angiogenesis by targeting vascular endothelial growth factor receptor 2 signaling

  • Authors:
    • Soojung Jin
    • Hee Jung Yun
    • Hyun Young Jeong
    • You Na Oh
    • Hyun‑Jin Park
    • Seung-Geun Yun
    • Byung Woo Kim
    • Hyun Ju Kwon
  • View Affiliations / Copyright

    Affiliations: Department of Life Science and Biotechnology, College of Natural Sciences and Human Ecology, Dong-Eui University, Busanjin-gu, Busan 614-714, Republic of Korea, Blue-Bio Industry Regional Innovation Center, Dong-Eui University, Busanjin-gu, Busan 614-714, Republic of Korea
  • Pages: 1178-1184
    |
    Published online on: June 24, 2015
       https://doi.org/10.3892/or.2015.4075
  • 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

Widdrol is an odorous compound derived from Juniperus chinensis that is widely used in traditional medicine to treat fever, inflammation and cancer. It was previously reported that widdrol has antitumor activity by apoptosis induction in cancer cells in vitro. However, its anti-angiogenic activity remains elusive. In the present study, we investigated the anti‑angiogenic activity of widdrol and the molecular mechanisms involved. Widdrol inhibited cell proliferation via G1 phase arrest induction in human umbilical vein endothelial cells (HUVECs) in a dose-dependent manner. Additionally, it was associated with a decreased expression of cyclin-dependent kinase 2 (CDK2) and an increased expression of p21, a CDK inhibitor. Widdrol significantly inhibited the cell migration and tube formation of HUVECs using an in vitro angiogenesis assay. The results showed that widdrol suppressed phosphorylation of vascular endothelial growth factor receptor 2 (VEGFR2) and its downstream proteins, such as AKT, focal adhesion kinase (FAK) and endothelial nitric oxide synthase (eNOS). Moreover, widdrol effectively reduced tumor growth and blood vessel formation in colon tumor xenograft mice. Collectively, these results suggested that widdrol may act as a potential anti-angiogenic agent by inhibiting vessel sprouting and growth, which may have implications for angioprevention.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Folkman J: Tumor angiogenesis: Therapeutic implications. N Engl J Med. 285:1182–1186. 1971. View Article : Google Scholar : PubMed/NCBI

2 

Kerbel RS: Tumor angiogenesis: Past, present and the near future. Carcinogenesis. 21:505–515. 2000. View Article : Google Scholar : PubMed/NCBI

3 

Alon T, Hemo I, Itin A, Pe'er J, Stone J and Keshet E: Vascular endothelial growth factor acts as a survival factor for newly formed retinal vessels and has implications for retinopathy of prematurity. Nat Med. 1:1024–1028. 1995. View Article : Google Scholar : PubMed/NCBI

4 

Ferrara N: Vascular endothelial growth factor: Molecular and biological aspects. Curr Top Microbiol Immunol. 237:1–30. 1999.PubMed/NCBI

5 

Dvorak HF, Brown LF, Detmar M and Dvorak AM: Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis. Am J Pathol. 146:1029–1039. 1995.PubMed/NCBI

6 

Dimmeler S, Fleming I, Fisslthaler B, Hermann C, Busse R and Zeiher AM: Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation. Nature. 399:601–605. 1999. View Article : Google Scholar : PubMed/NCBI

7 

Olsson AK, Dimberg A, Kreuger J and Claesson-Welsh L: VEGF receptor signalling - in control of vascular function. Nat Rev Mol Cell Biol. 7:359–371. 2006. View Article : Google Scholar : PubMed/NCBI

8 

Ferrara N and Kerbel RS: Angiogenesis as a therapeutic target. Nature. 438:967–974. 2005. View Article : Google Scholar : PubMed/NCBI

9 

Zheng X, Li A, Zhao L, Zhou T, Shen Q, Cui Q and Qin X: Key role of microRNA-15a in the KLF4 suppressions of proliferation and angiogenesis in endothelial and vascular smooth muscle cells. Biochem Biophys Res Commun. 437:625–631. 2013. View Article : Google Scholar : PubMed/NCBI

10 

Roberts JM, Koff A, Polyak K, Firpo E, Collins S, Ohtsubo M and Massagué J: Cyclins, Cdks, and cyclin kinase inhibitors. Cold Spring Harb Symp Quant Biol. 59:31–38. 1994. View Article : Google Scholar : PubMed/NCBI

11 

Sherr CJ and Roberts JM: CDK inhibitors: Positive and negative regulators of G1-phase progression. Genes Dev. 13:1501–1512. 1999. View Article : Google Scholar : PubMed/NCBI

12 

Kwon HJ, Hong YK, Park C, Choi YH, Yun HJ, Lee EW and Kim BW: Widdrol induces cell cycle arrest, associated with MCM down-regulation, in human colon adenocarcinoma cells. Cancer Lett. 290:96–103. 2010. View Article : Google Scholar

13 

Kwon HJ, Lee EW, Hong YK, Yun HJ and Kim BW: Widdrol from Juniperus chinensis induces apoptosis in human colon adenocarcinoma HT29 cells. Biotechnol Bioprocess Eng. 15:167–172. 2010. View Article : Google Scholar

14 

Martínez-Poveda B, Muñoz-Chápuli R, Rodríguez-Nieto S, Quintela JM, Fernández A, Medina MA and Quesada AR: IB05204, a dichloropyridodithienotriazine, inhibits angiogenesis in vitro and in vivo. Mol Cancer Ther. 6:2675–2685. 2007. View Article : Google Scholar : PubMed/NCBI

15 

Argov M, Kashi R, Peer D and Margalit R: Treatment of resistant human colon cancer xenografts by a fluoxetine-doxorubicin combination enhances therapeutic responses comparable to an aggressive bevacizumab regimen. Cancer Lett. 274:118–125. 2009. View Article : Google Scholar

16 

Folkman J: Role of angiogenesis in tumor growth and metastasis. Semin Oncol. 29(Suppl 16): 15–18. 2002. View Article : Google Scholar

17 

He D, Jin J, Zheng Y, Bruce IC, Tam S and Ma X: Anti-angiogenesis effect of trichosanthin and the underlying mechanism. Biochem Biophys Res Commun. 430:735–740. 2013. View Article : Google Scholar

18 

Rössler J, Taylor M, Geoerger B, Farace F, Lagodny J, Peschka-Süss R, Niemeyer CM and Vassal G: Angiogenesis as a target in neuroblastoma. Eur J Cancer. 44:1645–1656. 2008. View Article : Google Scholar : PubMed/NCBI

19 

Shizukuda Y, Tang S, Yokota R and Ware JA: Vascular endothelial growth factor-induced endothelial cell migration and proliferation depend on a nitric oxide-mediated decrease in protein kinase Cdelta activity. Circ Res. 85:247–256. 1999. View Article : Google Scholar : PubMed/NCBI

20 

Taimeh Z, Loughran J, Birks EJ and Bolli R: Vascular endothelial growth factor in heart failure. Nat Rev Cardiol. 10:519–530. 2013. View Article : Google Scholar : PubMed/NCBI

21 

Eskens FA and Verweij J: The clinical toxicity profile of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor (VEGFR) targeting angiogenesis inhibitors; a review. Eur J Cancer. 42:3127–3139. 2006. View Article : Google Scholar : PubMed/NCBI

22 

Saraswati S, Kanaujia PK, Kumar S, Kumar R and Alhaider AA: Tylophorine, a phenanthraindolizidine alkaloid isolated from Tylophora indica exerts antiangiogenic and antitumor activity by targeting vascular endothelial growth factor receptor 2-mediated angiogenesis. Mol Cancer. 12:822013. View Article : Google Scholar : PubMed/NCBI

23 

Takahashi S: Vascular endothelial growth factor (VEGF), VEGF receptors and their inhibitors for antiangiogenic tumor therapy. Biol Pharm Bull. 34:1785–1788. 2011. View Article : Google Scholar : PubMed/NCBI

24 

Cheng JQ, Lindsley CW, Cheng GZ, Yang H and Nicosia SV: The Akt/PKB pathway: Molecular target for cancer drug discovery. Oncogene. 24:7482–7492. 2005. View Article : Google Scholar : PubMed/NCBI

25 

Jiang BH and Liu LZ: AKT signaling in regulating angiogenesis. Curr Cancer Drug Targets. 8:19–26. 2008. View Article : Google Scholar : PubMed/NCBI

26 

Yue GG, Chan BC, Kwok HF, Wong YL, Leung HW, Ji CJ, Fung KP, Leung PC, Tan NH and Lau CB: Anti-angiogenesis and immunomodulatory activities of an anti-tumor sesquiterpene bigelovin isolated from Inula helianthus-aquatica. Eur J Med Chem. 59:243–252. 2013. View Article : Google Scholar

27 

Hong SW, Jung KH, Lee HS, Son MK, Yan HH, Kang NS, Lee J and Hong SS: SB365, Pulsatilla saponin D, targets c-Met and exerts antiangiogenic and antitumor activities. Carcinogenesis. 34:2156–2169. 2013. View Article : Google Scholar : PubMed/NCBI

28 

Wang Y, Ma W and Zheng W: Deguelin, a novel anti-tumorigenic agent targeting apoptosis, cell cycle arrest and anti-angiogenesis for cancer chemoprevention. Mol Clin Oncol. 1:215–219. 2013.

29 

Xiao D and Singh SV: Phenethyl isothiocyanate inhibits angiogenesis in vitro and ex vivo. Cancer Res. 67:2239–2246. 2007. View Article : Google Scholar : PubMed/NCBI

30 

Liu JX, Luo MQ, Xia M, Wu Q, Long SM, Hu Y, Gao GC, Yao XL, He M, Su H, et al: Marine compound catunaregin inhibits angiogenesis through the modulation of phosphorylation of akt and eNOS in vivo and in vitro. Mar Drugs. 12:2790–2801. 2014. View Article : Google Scholar : PubMed/NCBI

31 

Favot L, Keravis T and Lugnier C: Modulation of VEGF-induced endothelial cell cycle protein expression through cyclic AMP hydrolysis by PDE2 and PDE4. Thromb Haemost. 92:634–645. 2004.PubMed/NCBI

32 

Shi F, Wang YC, Zhao TZ, Zhang S, Du TY, Yang CB, Li YH and Sun XQ: Effects of simulated microgravity on human umbilical vein endothelial cell angiogenesis and role of the PI3K-Akt-eNOS signal pathway. PLoS One. 7:e403652012. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Jin S, Yun HJ, Jeong HY, Oh YN, Park HJ, Yun S, Kim BW and Kwon HJ: Widdrol, a sesquiterpene isolated from Juniperus chinensis, inhibits angiogenesis by targeting vascular endothelial growth factor receptor 2 signaling. Oncol Rep 34: 1178-1184, 2015.
APA
Jin, S., Yun, H.J., Jeong, H.Y., Oh, Y.N., Park, H., Yun, S. ... Kwon, H.J. (2015). Widdrol, a sesquiterpene isolated from Juniperus chinensis, inhibits angiogenesis by targeting vascular endothelial growth factor receptor 2 signaling. Oncology Reports, 34, 1178-1184. https://doi.org/10.3892/or.2015.4075
MLA
Jin, S., Yun, H. J., Jeong, H. Y., Oh, Y. N., Park, H., Yun, S., Kim, B. W., Kwon, H. J."Widdrol, a sesquiterpene isolated from Juniperus chinensis, inhibits angiogenesis by targeting vascular endothelial growth factor receptor 2 signaling". Oncology Reports 34.3 (2015): 1178-1184.
Chicago
Jin, S., Yun, H. J., Jeong, H. Y., Oh, Y. N., Park, H., Yun, S., Kim, B. W., Kwon, H. J."Widdrol, a sesquiterpene isolated from Juniperus chinensis, inhibits angiogenesis by targeting vascular endothelial growth factor receptor 2 signaling". Oncology Reports 34, no. 3 (2015): 1178-1184. https://doi.org/10.3892/or.2015.4075
Copy and paste a formatted citation
x
Spandidos Publications style
Jin S, Yun HJ, Jeong HY, Oh YN, Park HJ, Yun S, Kim BW and Kwon HJ: Widdrol, a sesquiterpene isolated from Juniperus chinensis, inhibits angiogenesis by targeting vascular endothelial growth factor receptor 2 signaling. Oncol Rep 34: 1178-1184, 2015.
APA
Jin, S., Yun, H.J., Jeong, H.Y., Oh, Y.N., Park, H., Yun, S. ... Kwon, H.J. (2015). Widdrol, a sesquiterpene isolated from Juniperus chinensis, inhibits angiogenesis by targeting vascular endothelial growth factor receptor 2 signaling. Oncology Reports, 34, 1178-1184. https://doi.org/10.3892/or.2015.4075
MLA
Jin, S., Yun, H. J., Jeong, H. Y., Oh, Y. N., Park, H., Yun, S., Kim, B. W., Kwon, H. J."Widdrol, a sesquiterpene isolated from Juniperus chinensis, inhibits angiogenesis by targeting vascular endothelial growth factor receptor 2 signaling". Oncology Reports 34.3 (2015): 1178-1184.
Chicago
Jin, S., Yun, H. J., Jeong, H. Y., Oh, Y. N., Park, H., Yun, S., Kim, B. W., Kwon, H. J."Widdrol, a sesquiterpene isolated from Juniperus chinensis, inhibits angiogenesis by targeting vascular endothelial growth factor receptor 2 signaling". Oncology Reports 34, no. 3 (2015): 1178-1184. https://doi.org/10.3892/or.2015.4075
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