Inhibitory action of Celastrol on hypoxia-mediated angiogenesis and metastasis via the HIF-1α pathway

  • Authors:
    • Lili Huang
    • Zefu Zhang
    • Sheng Zhang
    • Jinghua Ren
    • Ruiguang Zhang
    • Hui Zeng
    • Qingfeng Li
    • Gang Wu
  • View Affiliations

  • Published online on: January 18, 2011     https://doi.org/10.3892/ijmm.2011.600
  • Pages: 407-415
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Abstract

Celastrol, a natural biologically active compound isolated from Tripterygium wilfordii Hook F root extracts, has been shown to possess antitumor properties and therefore, is an interesting candidate for the development of novel chemotherapeutic cancer agents. In this study, we have demonstrated that Celastrol is a potent inhibitor of hypoxia-induced angiogenic and metastatic activity as shown by a decrease in the proliferation of both endothelial and cancer cells, blocking of migration as well as of tube formation of endothelial cells, and by inhibition of cancer cell invasion under hypoxic conditions. Moreover, Celastrol decreased hypoxia-inducible factor-1α (HIF-1α) mRNA levels under both normoxia and hypoxia and inhibited hypoxia-induced accumulation of nuclear HIF-1α protein. Meanwhile, inhibition of nuclear HIF-1α protein levels were accompanied by a reduction in the transcriptional activity of HIF-1α target genes, including VEGF. In addition, the inhibitory effect of Celastrol on HIF-1α protein was partly due to its suppression of HSP90 activity. We conclude that Celastrol regulates HIF-1α at multiple levels that may together or individually contribute to its antitumor activity against hypoxia-induced angiogenesis and metastasis.

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March 2011
Volume 27 Issue 3

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Huang L, Zhang Z, Zhang S, Ren J, Zhang R, Zeng H, Li Q and Wu G: Inhibitory action of Celastrol on hypoxia-mediated angiogenesis and metastasis via the HIF-1α pathway. Int J Mol Med 27: 407-415, 2011.
APA
Huang, L., Zhang, Z., Zhang, S., Ren, J., Zhang, R., Zeng, H. ... Wu, G. (2011). Inhibitory action of Celastrol on hypoxia-mediated angiogenesis and metastasis via the HIF-1α pathway. International Journal of Molecular Medicine, 27, 407-415. https://doi.org/10.3892/ijmm.2011.600
MLA
Huang, L., Zhang, Z., Zhang, S., Ren, J., Zhang, R., Zeng, H., Li, Q., Wu, G."Inhibitory action of Celastrol on hypoxia-mediated angiogenesis and metastasis via the HIF-1α pathway". International Journal of Molecular Medicine 27.3 (2011): 407-415.
Chicago
Huang, L., Zhang, Z., Zhang, S., Ren, J., Zhang, R., Zeng, H., Li, Q., Wu, G."Inhibitory action of Celastrol on hypoxia-mediated angiogenesis and metastasis via the HIF-1α pathway". International Journal of Molecular Medicine 27, no. 3 (2011): 407-415. https://doi.org/10.3892/ijmm.2011.600