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

doi:10.1016/j.bbrc.2007.03.178

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

Toxicology and Cancer Biology

Research output: Contribution to journal › Article › peer-review

26 Scopus citations

Abstract

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 language	English
Pages (from-to)	517-523
Number of pages	7
Journal	Biochemical and Biophysical Research Communications
Volume	357
Issue number	2
DOIs	https://doi.org/10.1016/j.bbrc.2007.03.178
State	Published - 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.

Keywords

BPQ
HIF-1
Hsp90
VEGF

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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10.1016/j.bbrc.2007.03.178

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

abstract = "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.",

keywords = "BPQ, HIF-1, Hsp90, VEGF",

author = "Li, {Zhao Dong} and Liu, {Ling Zhi} and Xianglin Shi and Jing Fang and Jiang, {Bing Hua}",

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{\textquoteright}Angelo (The Institut de Pharmacologie Moleculaire et Cellulaire du, France) for kindly providing the ODD-GFP construct.",

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AU - Li, Zhao Dong

AU - Liu, Ling Zhi

AU - Shi, Xianglin

AU - Fang, Jing

AU - Jiang, Bing Hua

N1 - 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.

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N2 - 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.

AB - 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.

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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