Benzo[a]pyrene-3,6-dione inhibited VEGF expression through inducing HIF-1α degradation

Zhao Dong Li, Ling Zhi Liu, Xianglin Shi, Jing Fang, Bing Hua Jiang

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


Vascular endothelial growth factor (VEGF) is a potent angiogenesis inducer for tumor growth and angiogenesis. Benzo[a]pyrene (BaP) belongs to polycyclic aromatic hydrocarbons (PAHs) and is known to cause carcinogenesis. But the effects of BaP and its metabolites on VEGF and HIF-1 expression remain to be elucidated. In this study, we found benzo[a]pyrene-3,6-dione (BPQ), but not BaP and benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE) inhibited VEGF expression in a dose-dependent manner. BPQ inhibited VEGF transcriptional activation through hypoxia-inducible factor 1 (HIF-1) binding site. BPQ specifically decreased HIF-1α, but not HIF-1β subunit expression in A549 cells. We found that BPQ did not inhibit HIF-1α mRNA level, but inhibited its protein expression in a proteasome-dependent manner. To further clarify the mechanism of BPQ in regulating HIF-1α stability, we found that BPQ inhibited HIF-1α protein expression by the increase of the proteasome-dependent degradation, and by the disruption of HIF-1α and Hsp90 association.

Original languageEnglish
Pages (from-to)517-523
Number of pages7
JournalBiochemical and Biophysical Research Communications
Issue number2
StatePublished - Jun 1 2007

Bibliographical note

Funding Information:
This study was supported by research grants from National Natural Science Foundation of China (Nos. 30470361 and 30570962), from Philip Morris, USA, Inc., and from Shanghai Municipal Commission of Science and Technology (05DJ14009, 04DZ14007). We thank Dr. Gisela D’Angelo (The Institut de Pharmacologie Moleculaire et Cellulaire du, France) for kindly providing the ODD-GFP construct.


  • BPQ
  • HIF-1
  • Hsp90
  • VEGF

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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