Kamebakaurin inhibits the expression of hypoxia-inducible factor-1α and its target genes to confer antitumor activity

  • Authors:
    • Ke Si Wang
    • Juan Ma
    • Chunliu Mi
    • Jing Li
    • Jung Joon Lee
    • Xuejun Jin
  • View Affiliations

  • Published online on: January 19, 2016     https://doi.org/10.3892/or.2016.4576
  • Pages: 2045-2052
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Abstract

Hypoxia-inducible factor 1 (HIF-1), a heterodimeric transcription factor that mediates the adaptation of tumor cells and tissues to the hypoxic microenvironment, has attracted considerable interest as a potential therapeutic target. Kamebakaurin is a diterpenoid compound isolated from Isodon excia (Maxin.) Hara, which has been used for anti-inflammatory activities. However, its antitumor activity along with molecular mechanism has not been reported. Kamebakaurin showed potent inhibitory activity against HIF-1 activation induced by hypoxia or CoCl2 in various human cancer cell lines. This compound significantly decreased the hypoxia-induced accumulation of HIF-1α protein, whereas it did not affect the expression of topoisomerase-I (Topo-I). Further analysis revealed that kamebakaurin inhibited HIF-1α protein synthesis, without affecting the expression level of HIF-1α mRNA or degradation of HIF-1α protein. Furthermore, kamebakaurin prevented hypoxia-induced expression of HIF-1 target genes for vascular endothelial growth factor (VEGF) and erythropoietin (EPO). However, kamebakaurin caused cell growth inhibition via cell cycle arrest at G1 phase in tumor cells. In vivo studies, we further confirmed the inhibitory effect of kamebakaurin on the expression of HIF-1α proteins, leading to growth inhibition of HCT116 cells in a xenograft tumor model. These results show that kamebakaurin is an effective inhibitor of HIF-1 and provide new perspectives into its anticancer activity.
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April-2016
Volume 35 Issue 4

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Wang KS, Ma J, Mi C, Li J, Lee JJ and Jin X: Kamebakaurin inhibits the expression of hypoxia-inducible factor-1α and its target genes to confer antitumor activity. Oncol Rep 35: 2045-2052, 2016
APA
Wang, K.S., Ma, J., Mi, C., Li, J., Lee, J.J., & Jin, X. (2016). Kamebakaurin inhibits the expression of hypoxia-inducible factor-1α and its target genes to confer antitumor activity. Oncology Reports, 35, 2045-2052. https://doi.org/10.3892/or.2016.4576
MLA
Wang, K. S., Ma, J., Mi, C., Li, J., Lee, J. J., Jin, X."Kamebakaurin inhibits the expression of hypoxia-inducible factor-1α and its target genes to confer antitumor activity". Oncology Reports 35.4 (2016): 2045-2052.
Chicago
Wang, K. S., Ma, J., Mi, C., Li, J., Lee, J. J., Jin, X."Kamebakaurin inhibits the expression of hypoxia-inducible factor-1α and its target genes to confer antitumor activity". Oncology Reports 35, no. 4 (2016): 2045-2052. https://doi.org/10.3892/or.2016.4576