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

Producción científica: Article › revisión exhaustiva

29 Citas (Scopus)

Resumen

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.

Idioma original	English
Páginas (desde-hasta)	517-523
Número de páginas	7
Publicación	Biochemical and Biophysical Research Communications
Volumen	357
N.º	2
DOI	https://doi.org/10.1016/j.bbrc.2007.03.178
Estado	Published - jun 1 2007

Nota bibliográfica

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.

Financiación

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.

Financiadores	Número del financiador
Philip Morris, USA, Inc.
National Natural Science Foundation of China (NSFC)	30570962, 30470361
Science and Technology Commission of Shanghai Municipality	04DZ14007, 05DJ14009

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 - Fang, Jing

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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

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Nota bibliográfica

Financiación

ASJC Scopus subject areas

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