TargetRx Atlas

MRNA basic information

  • mRNA ID:ENST00000337138
  • Gene Name:HIF1A
  • mRNA database:Ensembl
  • mRNA expression :down-regulated
  • mRNA Method:RT-PCR
  • mRNA Pathway:HIF-1 signaling pathway
  • Evidence:validated
  • (mRNA-drug)

Drug basic information

  • Drug ID:NA
  • Drug Name:Celastrol
  • Drug Method:down-regulated the gene expression the gene expression

Disease basic infommation

  • Disease:hepatocellular carcinoma
  • Tissue:cell lines (Hep3B, SK-Hep1,HeLa)

Other information

  • Title:Celastrol inhibits the HIF-1alpha pathway by inhibition of mTOR/p70S6K/eIF4E and ERK1/2 phosphorylation in human hepatoma cells
  • Journal:Oncol Rep
  • Published:2014
  • PubMed ID:24859482
  • Abstract:Hypoxia-inducible factor-1 (HIF-1) is the central mediator of cellular responses to low oxygen and vital to many aspects of cancer biology. In a search for HIF-1 inhibitors, we identified celastrol as an inhibitor of HIF-1 activation from Tripterygium wilfordii. In the present study, we demonstrated the effect of celastrol on HIF-1 activation. Celastrol showed a potent inhibitory activity against HIF-1 activation induced by hypoxia in various human cancer cell lines. This compound markedly decreased the hypoxia-induced accumulation of HIF-1α protein dose-dependently, whereas it did not affect the expressions of HIF-1β and topoisomerase-I (topo-I). Furthermore, celastrol prevented hypoxia-induced expression of HIF-1 target genes for vascular endothelial growth factor (VEGF) and erythropoietin (EPO). Further analysis revealed that celastrol inhibited HIF-1α protein synthesis, without affecting the expression level of HIF-1α mRNA or degradation of HIF-1α protein. Markedly, we found that suppression of HIF-1α accumulation by celastrol correlated with strong dephosphorylation of mammalian target of rapamycin (mTOR) and its effectors, ribosomal protein S6 kinase (p70S6K) and eukaryotic initiation factor 4E (eIF4E) and extracellular signal-regulated kinase (ERK), pathways known to regulate HIF-1α expression at the translational level. In vivo studies further confirmed the inhibitory effect of celastrol on the expression of HIF-1α proteins, leading to a decreased growth of Hep3B cells in a xenograft tumor model. Our data suggested that celastrol is an effective inhibitor of HIF-1 and provide new perspectives into the mechanism of its anticancer activity.
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