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
July-2015 Volume 34 Issue 1

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
July-2015 Volume 34 Issue 1

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

M410, a combretastatin A4 analogue, disrupts microtubules and inhibits HIF-1α in human breast cancer cells

  • Authors:
    • Hang Yang
    • Qing Xia
    • Yong Zou
    • Kefeng Wang
    • Wenqi Jiang
    • Yuchen Cai
  • View Affiliations / Copyright

    Affiliations: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China, Department of Oncology, Shanghai Jiaotong University Affiliated First People's Hospital, Shanghai 201620, P.R. China, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Guangdong 510006, P.R. China
  • Pages: 334-340
    |
    Published online on: May 12, 2015
       https://doi.org/10.3892/or.2015.3975
  • 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

Hypoxia-inducible factor-1 (HIF-1) is a primary transcriptional factor that targets a series of genes participating in angiogenesis and cell proliferation. HIF-1 is a heterodimer consisting of a constitutively-expressed HIF-1β subunit and an oxygen-regulated HIF-1α subunit. Overexpression of HIF-1α has been found in various types of cancer. Targeting HIF-1α may be a novel approach to cancer therapy. Previous findings showed that a newly synthesized compound (Z)-3,4',5-trimethoxylstilbene-3'-O-phosphate disodium (M410), an analogue of the microtubule-targeting agent, combretastatin A4, inhibited the polymerization of bovine brain tubulin and induced mitotic arrest. The aim of the present study was to determine the mechanism of M410 destabilizes microtubules and inhibits HIF-1α in breast cancer cells. We performed 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, immunofluorescence and confocal microscopy, ELISA assay, transient transfections and reporter gene assay, immunoblot analysis and isolation and analysis of RNA to evaluate the mechanisms of M410 on breast cancer. SPSS 17.0 was used to analyze the data. The results showed that the growth of breast cancer cells was inhibited in a dose-dependent manner. MDA-MB-231 was the most sensitive, with a 50% growth inhibition (GI50) of 111.4±2.2 nM. HIF-1α expression was clearly reduced following M410 treatment in a dose-dependent manner. M410 downregulated the nuclear accumulation of HIF-1α, and the strong correlation between disruption of the microtubule cytoskeleton and the inhibition of HIF-1α expression was independent of mitotic arrest. Furthermore, M410 inhibited HIF-1α at the post‑transcriptional level and inhibited the vascular endothelial growth factor (VEGF) at the transcription level. M410 downregulated HIF-1α expression in a proteasome-independent manner. In conclusion, M410 depolymerized microtubules and downregulated HIF-1α protein levels in a proteasome-independent manner and reduced the mRNA of HIF-1-targeted genes in the MDA-MB-231 breast cancer cell line.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Althuis MD, Dozier JM, Anderson WF, Devesa SS and Brinton LA: Global trends in breast cancer incidence and mortality 1973–1997. Int J Epidemiol. 34:405–412. 2005. View Article : Google Scholar : PubMed/NCBI

2 

Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar : PubMed/NCBI

3 

Forbes JF: The incidence of breast cancer: the global burden, public health considerations. Semin Oncol. 24(Suppl 1): S1–20–S1–35. 1997.

4 

Rakha EA, El-Sayed ME, Green AR, Lee AH, Robertson JF and Ellis IO: Prognostic markers in triple-negative breast cancer. Cancer. 109:25–32. 2007. View Article : Google Scholar

5 

Dent R, Trudeau M, Pritchard KI, Hanna WM, Kahn HK, Sawka CA, Lickley LA, Rawlinson E, Sun P and Narod SA: Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res. 13:4429–4434. 2007. View Article : Google Scholar : PubMed/NCBI

6 

Foulkes WD, Smith IE and Reis-Filho JS: Triple-negative breast cancer. N Engl J Med. 363:1938–1948. 2010. View Article : Google Scholar : PubMed/NCBI

7 

Hudis CA and Gianni L: Triple-negative breast cancer: an unmet medical need. Oncologist. 16(Suppl 1): 1–11. 2011. View Article : Google Scholar : PubMed/NCBI

8 

Kaelin WG Jr and Ratcliffe PJ: Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway. Mol Cell. 30:393–402. 2008. View Article : Google Scholar : PubMed/NCBI

9 

Zhong H, De Marzo AM, Laughner E, Lim M, Hilton DA, Zagzag D, Buechler P, Isaacs WB, Semenza GL and Simons JW: Overexpression of hypoxia-inducible factor 1alpha in common human cancers and their metastases. Cancer Res. 59:5830–5835. 1999.PubMed/NCBI

10 

Sun HC, Qiu ZJ, Liu J, Sun J, Jiang T, Huang KJ, Yao M and Huang C: Expression of hypoxia-inducible factor-1α and associated proteins in pancreatic ductal adenocarcinoma and their impact on prognosis. Int J Oncol. 30:1359–1367. 2007.PubMed/NCBI

11 

Rasheed S, Harris AL, Tekkis PP, Turley H, Silver A, McDonald PJ, Talbot IC, Glynne-Jones R, Northover JM and Guenther T: Hypoxia-inducible factor-1alpha and -2alpha are expressed in most rectal cancers but only hypoxia-inducible factor-1alpha is associated with prognosis. Br J Cancer. 100:1666–1673. 2009. View Article : Google Scholar : PubMed/NCBI

12 

Conley SJ, Gheordunescu E, Kakarala P, Newman B, Korkaya H, Heath AN, Clouthier SG and Wicha MS: Antiangiogenic agents increase breast cancer stem cells via the generation of tumor hypoxia. Proc Natl Acad Sci uSA. 109:2784–2789. 2012. View Article : Google Scholar : PubMed/NCBI

13 

Papandreou I, Cairns RA, Fontana L, Lim AL and Denko NC: HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption. Cell Metab. 3:187–197. 2006. View Article : Google Scholar : PubMed/NCBI

14 

Mikstacka R, Stefański T and Różański J: Tubulin-interactive stilbene derivatives as anticancer agents. Cell Mol Biol Lett. 18:368–397. 2013. View Article : Google Scholar : PubMed/NCBI

15 

Cai YC, Zou Y, Ye YL, Sun HY, Su QG, Wang ZX, Zeng ZL and Xian LJ: Anti-tumor activity and mechanisms of a novel vascular disrupting agent, (Z)-3,4′,5-trimethoxylstilbene-3′-O-phosphate disodium (M410). Invest New Drugs. 29:300–311. 2011. View Article : Google Scholar

16 

Wilson WR and Hay MP: Targeting hypoxia in cancer therapy. Nat Rev Cancer. 11:393–410. 2011. View Article : Google Scholar : PubMed/NCBI

17 

Vaupel P, Mayer A and Höckel M: Tumor hypoxia and malignant progression. Methods Enzymol. 381:335–354. 2004. View Article : Google Scholar : PubMed/NCBI

18 

Gong L, Zhang W, Zhou J, Lu J, Xiong H, Shi X and Chen J: Prognostic value of HIFs expression in head and neck cancer: a systematic review. PLoS One. 8:e750942013. View Article : Google Scholar : PubMed/NCBI

19 

Semenza GL: Defining the role of hypoxia-inducible factor 1 in cancer biology and therapeutics. Oncogene. 29:625–634. 2010. View Article : Google Scholar :

20 

van der Groep P, Bouter A, Menko FH, van der Wall E and van Diest PJ: High frequency of HIF-1alpha overexpression in BRCA1 related breast cancer. Breast Cancer Res Treat. 111:475–480. 2008. View Article : Google Scholar

21 

Bos R, van der Groep P, Greijer AE, Shvarts A, Meijer S, Pinedo HM, Semenza GL, van Diest PJ and van der Wall E: Levels of hypoxia-inducible factor-1α independently predict prognosis in patients with lymph node negative breast carcinoma. Cancer. 97:1573–1581. 2003. View Article : Google Scholar : PubMed/NCBI

22 

Schindl M, Schoppmann SF, Samonigg H, Hausmaninger H, Kwasny W, Gnant M, Jakesz R, Kubista E, Birner P and Oberhuber G; Austrian Breast and Colorectal Cancer Study Group: Overexpression of hypoxia-inducible factor 1α is associated with an unfavorable prognosis in lymph node-positive breast cancer. Clin Cancer Res. 8:1831–1837. 2002.PubMed/NCBI

23 

Semenza GL: Targeting HIF-1 for cancer therapy. Nat Rev Cancer. 3:721–732. 2003. View Article : Google Scholar : PubMed/NCBI

24 

Welsh S, Williams R, Kirkpatrick L, Paine-Murrieta G and Powis G: Antitumor activity and pharmacodynamic properties of PX-478, an inhibitor of hypoxia-inducible factor-1alpha. Mol Cancer Ther. 3:233–244. 2004.PubMed/NCBI

25 

Kong D, Park EJ, Stephen AG, Calvani M, Cardellina JH, Monks A, Fisher RJ, Shoemaker RH and Melillo G: Echi-nomycin, a small-molecule inhibitor of hypoxia-inducible factor-1 DNA-binding activity. Cancer Res. 65:9047–9055. 2005. View Article : Google Scholar : PubMed/NCBI

26 

Kim KH, Jung HJ and Kwon HJ: A new anti-angiogenic small molecule, G0811, inhibits angiogenesis via targeting hypoxia inducible factor (HIF)-1α signal transduction. Biochem Biophys Res Commun. 441:399–404. 2013. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Yang H, Xia Q, Zou Y, Wang K, Jiang W and Cai Y: M410, a combretastatin A4 analogue, disrupts microtubules and inhibits HIF-1α in human breast cancer cells. Oncol Rep 34: 334-340, 2015.
APA
Yang, H., Xia, Q., Zou, Y., Wang, K., Jiang, W., & Cai, Y. (2015). M410, a combretastatin A4 analogue, disrupts microtubules and inhibits HIF-1α in human breast cancer cells. Oncology Reports, 34, 334-340. https://doi.org/10.3892/or.2015.3975
MLA
Yang, H., Xia, Q., Zou, Y., Wang, K., Jiang, W., Cai, Y."M410, a combretastatin A4 analogue, disrupts microtubules and inhibits HIF-1α in human breast cancer cells". Oncology Reports 34.1 (2015): 334-340.
Chicago
Yang, H., Xia, Q., Zou, Y., Wang, K., Jiang, W., Cai, Y."M410, a combretastatin A4 analogue, disrupts microtubules and inhibits HIF-1α in human breast cancer cells". Oncology Reports 34, no. 1 (2015): 334-340. https://doi.org/10.3892/or.2015.3975
Copy and paste a formatted citation
x
Spandidos Publications style
Yang H, Xia Q, Zou Y, Wang K, Jiang W and Cai Y: M410, a combretastatin A4 analogue, disrupts microtubules and inhibits HIF-1α in human breast cancer cells. Oncol Rep 34: 334-340, 2015.
APA
Yang, H., Xia, Q., Zou, Y., Wang, K., Jiang, W., & Cai, Y. (2015). M410, a combretastatin A4 analogue, disrupts microtubules and inhibits HIF-1α in human breast cancer cells. Oncology Reports, 34, 334-340. https://doi.org/10.3892/or.2015.3975
MLA
Yang, H., Xia, Q., Zou, Y., Wang, K., Jiang, W., Cai, Y."M410, a combretastatin A4 analogue, disrupts microtubules and inhibits HIF-1α in human breast cancer cells". Oncology Reports 34.1 (2015): 334-340.
Chicago
Yang, H., Xia, Q., Zou, Y., Wang, K., Jiang, W., Cai, Y."M410, a combretastatin A4 analogue, disrupts microtubules and inhibits HIF-1α in human breast cancer cells". Oncology Reports 34, no. 1 (2015): 334-340. https://doi.org/10.3892/or.2015.3975
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