Dibenzoylmethane, a natural dietary compound, induces HIF-1α and increases expression of VEGF

Nicola J. Mabjeesh; Margaret T. Willard; Wayne B. Harris; He Ying Sun; Ruoxiang Wang; Hua Zhong; Jay N. Umbreit; Jonathan W. Simons

doi:10.1016/S0006-291X(03)00336-X

Dibenzoylmethane, a natural dietary compound, induces HIF-1α and increases expression of VEGF

Nicola J. Mabjeesh, Margaret T. Willard, Wayne B. Harris, He Ying Sun, Ruoxiang Wang, Hua Zhong, Jay N. Umbreit^*, Jonathan W. Simons

^*Corresponding author for this work

Emory University

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

41 Scopus citations

Abstract

Hypoxia-inducible factor 1 (HIF-1) is the major transcription factor activated during hypoxia. It is composed of HIF-1α and HIF-1β subunits. While HIF-1β is constitutively expressed, HIF-1α is targeted to proteasome degradation under normoxic conditions. Under hypoxia, HIF-1α is stabilized and heterodimerizes with HIF-1β. Iron chelators have also been reported to stabilize HIF-1α protein and activate HIF-1. In this study, we investigated the effects of dibenzoylmethane (DBM), a natural dietary compound and an iron chelator, on HIF-1 pathway. We found that DBM increases HIF-1α protein levels in a dose- and time-dependent manner. This induction was accompanied with activation of HIF-1, measured by reporter gene assay and increased production of its downstream target, the vascular endothelial growth factor. Mechanistically, HIF-1α was stabilized by DBM at a step prior to ubiquitination. The effect of DBM on HIF-1 and its low toxicity profile might be therapeutically beneficial in ischemic diseases.

Original language	English
Pages (from-to)	279-286
Number of pages	8
Journal	Biochemical and Biophysical Research Communications
Volume	303
Issue number	1
DOIs	https://doi.org/10.1016/S0006-291X(03)00336-X
State	Published - 28 Mar 2003
Externally published	Yes

Funding

Funders	Funder number
CaP CURE Foundation
National Institutes of Health
National Cancer Institute	P50CA058236
Avon Foundation for Women
American Physicians Fellowship for Medicine in Israel

Keywords

Cardiomyocyte
Dibenzoylmethane
HIF-1α
Prostate cancer cells
VEGF

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/S0006-291X(03)00336-X

Cite this

@article{d58256997c4445b482c128b245ee6a9b,

title = "Dibenzoylmethane, a natural dietary compound, induces HIF-1α and increases expression of VEGF",

abstract = "Hypoxia-inducible factor 1 (HIF-1) is the major transcription factor activated during hypoxia. It is composed of HIF-1α and HIF-1β subunits. While HIF-1β is constitutively expressed, HIF-1α is targeted to proteasome degradation under normoxic conditions. Under hypoxia, HIF-1α is stabilized and heterodimerizes with HIF-1β. Iron chelators have also been reported to stabilize HIF-1α protein and activate HIF-1. In this study, we investigated the effects of dibenzoylmethane (DBM), a natural dietary compound and an iron chelator, on HIF-1 pathway. We found that DBM increases HIF-1α protein levels in a dose- and time-dependent manner. This induction was accompanied with activation of HIF-1, measured by reporter gene assay and increased production of its downstream target, the vascular endothelial growth factor. Mechanistically, HIF-1α was stabilized by DBM at a step prior to ubiquitination. The effect of DBM on HIF-1 and its low toxicity profile might be therapeutically beneficial in ischemic diseases.",

keywords = "Cardiomyocyte, Dibenzoylmethane, HIF-1α, Prostate cancer cells, VEGF",

author = "Mabjeesh, {Nicola J.} and Willard, {Margaret T.} and Harris, {Wayne B.} and Sun, {He Ying} and Ruoxiang Wang and Hua Zhong and Umbreit, {Jay N.} and Simons, {Jonathan W.}",

note = "Funding Information: This work was supported by NIH Prostate Cancer SPORE Grant CA-58236 (to J.W.S.), Avon Foundation (to J.W.S. and H.Z.), and CaP CURE Foundation (to J.W.S.). N.J.M. is a recipient of a fellowship from The American Physicians Fellowship for Medicine in Israel. We kindly thank Ms. Chomeka E. Marshall, M.Sc. for a critical reading of the manuscript.",

year = "2003",

month = mar,

day = "28",

doi = "10.1016/S0006-291X(03)00336-X",

language = "אנגלית",

volume = "303",

pages = "279--286",

journal = "Biochemical and Biophysical Research Communications",

issn = "0006-291X",

publisher = "Elsevier B.V.",

number = "1",

}

TY - JOUR

T1 - Dibenzoylmethane, a natural dietary compound, induces HIF-1α and increases expression of VEGF

AU - Mabjeesh, Nicola J.

AU - Willard, Margaret T.

AU - Harris, Wayne B.

AU - Sun, He Ying

AU - Wang, Ruoxiang

AU - Zhong, Hua

AU - Umbreit, Jay N.

AU - Simons, Jonathan W.

N1 - Funding Information: This work was supported by NIH Prostate Cancer SPORE Grant CA-58236 (to J.W.S.), Avon Foundation (to J.W.S. and H.Z.), and CaP CURE Foundation (to J.W.S.). N.J.M. is a recipient of a fellowship from The American Physicians Fellowship for Medicine in Israel. We kindly thank Ms. Chomeka E. Marshall, M.Sc. for a critical reading of the manuscript.

PY - 2003/3/28

Y1 - 2003/3/28

N2 - Hypoxia-inducible factor 1 (HIF-1) is the major transcription factor activated during hypoxia. It is composed of HIF-1α and HIF-1β subunits. While HIF-1β is constitutively expressed, HIF-1α is targeted to proteasome degradation under normoxic conditions. Under hypoxia, HIF-1α is stabilized and heterodimerizes with HIF-1β. Iron chelators have also been reported to stabilize HIF-1α protein and activate HIF-1. In this study, we investigated the effects of dibenzoylmethane (DBM), a natural dietary compound and an iron chelator, on HIF-1 pathway. We found that DBM increases HIF-1α protein levels in a dose- and time-dependent manner. This induction was accompanied with activation of HIF-1, measured by reporter gene assay and increased production of its downstream target, the vascular endothelial growth factor. Mechanistically, HIF-1α was stabilized by DBM at a step prior to ubiquitination. The effect of DBM on HIF-1 and its low toxicity profile might be therapeutically beneficial in ischemic diseases.

AB - Hypoxia-inducible factor 1 (HIF-1) is the major transcription factor activated during hypoxia. It is composed of HIF-1α and HIF-1β subunits. While HIF-1β is constitutively expressed, HIF-1α is targeted to proteasome degradation under normoxic conditions. Under hypoxia, HIF-1α is stabilized and heterodimerizes with HIF-1β. Iron chelators have also been reported to stabilize HIF-1α protein and activate HIF-1. In this study, we investigated the effects of dibenzoylmethane (DBM), a natural dietary compound and an iron chelator, on HIF-1 pathway. We found that DBM increases HIF-1α protein levels in a dose- and time-dependent manner. This induction was accompanied with activation of HIF-1, measured by reporter gene assay and increased production of its downstream target, the vascular endothelial growth factor. Mechanistically, HIF-1α was stabilized by DBM at a step prior to ubiquitination. The effect of DBM on HIF-1 and its low toxicity profile might be therapeutically beneficial in ischemic diseases.

KW - Cardiomyocyte

KW - Dibenzoylmethane

KW - HIF-1α

KW - Prostate cancer cells

KW - VEGF

UR - http://www.scopus.com/inward/record.url?scp=0037470774&partnerID=8YFLogxK

U2 - 10.1016/S0006-291X(03)00336-X

DO - 10.1016/S0006-291X(03)00336-X

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

C2 - 12646199

AN - SCOPUS:0037470774

SN - 0006-291X

VL - 303

SP - 279

EP - 286

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

IS - 1

ER -

Dibenzoylmethane, a natural dietary compound, induces HIF-1α and increases expression of VEGF

Abstract

Funding

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this