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Article

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 / Copyright

    Affiliations: Key Laboratory of Natural Resources of Changbai Mountain and Functional Molecules, Ministry of Education, Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji, Jilin 133002, P.R. China
  • Pages: 2045-2052
    |
    Published online on: January 19, 2016
       https://doi.org/10.3892/or.2016.4576
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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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1 

Danquah MK, Zhang XA and Mahato RI: Extravasation of polymeric nanomedicines across tumor vasculature. Adv Drug Deliv Rev. 63:623–639. 2011. View Article : Google Scholar

2 

Dewhirst MW, Cao Y and Moeller B: Cycling hypoxia and free radicals regulate angiogenesis and radiotherapy response. Nat Rev Cancer. 8:425–437. 2008. View Article : Google Scholar : PubMed/NCBI

3 

Brahimi-Horn MC, Chiche J and Pouysségur J: Hypoxia and cancer. J Mol Med Berl. 85:1301–1307. 2007. View Article : Google Scholar : PubMed/NCBI

4 

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

5 

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

6 

Wang GL, Jiang BH, Rue EA and Semenza GL: Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Proc Natl Acad Sci USA. 92:5510–5514. 1995. View Article : Google Scholar

7 

Jaakkola P, Mole DR, Tian YM, Wilson MI, Gielbert J, Gaskell SJ, von Kriegsheim A, Hebestreit HF, Mukherji M, Schofield CJ, et al: Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation. Science. 292:468–472. 2001. View Article : Google Scholar : PubMed/NCBI

8 

Wang GL and Semenza GL: Purification and characterization of hypoxia-inducible factor 1. J Biol Chem. 270:1230–1237. 1995. View Article : Google Scholar : PubMed/NCBI

9 

Rankin EB and Giaccia AJ: The role of hypoxia-inducible factors in tumorigenesis. Cell Death Differ. 15:678–685. 2008. View Article : Google Scholar : PubMed/NCBI

10 

Tsuzuki Y, Fukumura D, Oosthuyse B, Koike C, Carmeliet P and Jain RK: Vascular endothelial growth factor (VEGF) modulation by targeting hypoxia-inducible factor-1alpha--> hypoxia response element--> VEGF cascade differentially regulates vascular response and growth rate in tumors. Cancer Res. 60:6248–6252. 2000.PubMed/NCBI

11 

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

12 

Kim BW, Koppula S, Kim IS, Lim HW, Hong SM, Han SD, Hwang BY and Choi DK: Anti-neuroinflammatory activity of Kamebakaurin from Isodon japonicus via inhibition of c-Jun NH(2)-terminal kinase and p38 mitogen-activated protein kinase pathway in activated microglial cells. J Pharmacol Sci. 116:296–308. 2011. View Article : Google Scholar

13 

Lee JH, Choi JK, Noh MS, Hwang BY, Hong YS and Lee JJ: Anti-inflammatory effect of kamebakaurin in in vivo animal models. Planta Med. 70:526–530. 2004. View Article : Google Scholar : PubMed/NCBI

14 

Hervouet E, Cízková A, Demont J, Vojtísková A, Pecina P, Franssen-van Hal NL, Keijer J, Simonnet H, Ivánek R, Kmoch S, et al: HIF and reactive oxygen species regulate oxidative phosphorylation in cancer. Carcinogenesis. 29:1528–1537. 2008. View Article : Google Scholar : PubMed/NCBI

15 

Cai XF, Jin X, Lee D, Yang YT, Lee K, Hong YS, Lee JH and Lee JJ: Phenanthroquinolizidine alkaloids from the roots of Boehmeria pannosa potently inhibit hypoxia-inducible factor-1 in AGS human gastric cancer cells. J Nat Prod. 69:1095–1097. 2006. View Article : Google Scholar : PubMed/NCBI

16 

Li L, Dai HJ, Ye M, Wang SL, Xiao XJ, Zheng J, Chen HY, Luo YH and Liu J: Lycorine induces cell-cycle arrest in the G0/G1 phase in K562 cells via HDAC inhibition. Cancer Cell Int. 12:492012. View Article : Google Scholar : PubMed/NCBI

17 

Vaupel P and Mayer A: Hypoxia in cancer: Significance and impact on clinical outcome. Cancer Metastasis Rev. 26:225–239. 2007. View Article : Google Scholar : PubMed/NCBI

18 

Obermair A, Bancher-Todesca D, Bilgi S, Kaider A, Kohlberger P, Müllauer-Ertl S, Leodolter S and Gitsch G: Correlation of vascular endothelial growth factor expression and microvessel density in cervical intraepithelial neoplasia. J Natl Cancer Inst. 89:1212–1217. 1997. View Article : Google Scholar : PubMed/NCBI

19 

Tseng PL, Tai MH, Huang CC, Wang CC, Lin JW, Hung CH, Chen CH, Wang JH, Lu SN, Lee CM, et al: Overexpression of VEGF is associated with positive p53 immunostaining in hepato-cellular carcinoma (HCC) and adverse outcome of HCC patients. J Surg Oncol. 98:349–357. 2008. View Article : Google Scholar : PubMed/NCBI

20 

Maxwell PH, Dachs GU, Gleadle JM, Nicholls LG, Harris AL, Stratford IJ, Hankinson O, Pugh CW and Ratcliffe PJ: Hypoxia-inducible factor-1 modulates gene expression in solid tumors and influences both angiogenesis and tumor growth. Proc Natl Acad Sci USA. 94:8104–8109. 1997. View Article : Google Scholar : PubMed/NCBI

21 

Musgrove EA, Caldon CE, Barraclough J, Stone A and Sutherland RL: Cyclin D as a therapeutic target in cancer. Nat Rev Cancer. 11:558–572. 2011. View Article : Google Scholar : PubMed/NCBI

22 

Dang CV: MYC on the path to cancer. Cell. 149:22–35. 2012. View Article : Google Scholar : PubMed/NCBI

23 

Denis N, Kitzis A, Kruh J, Dautry F and Corcos D: Stimulation of methotrexate resistance and dihydrofolate reductase gene amplification by c-myc. Oncogene. 6:1453–1457. 1991.PubMed/NCBI

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Copy and paste a formatted citation
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
Copy and paste a formatted citation
x
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
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