Prostaglandin F2α induces the normoxic activation of the hypoxia-inducible factor-1 transcription factor in differentiating 3T3-L1 preadipocytes: Potential role in the regulation of adipogenesis

Rapid tumor growth is dependent on the capability of tumor blood vessels and glycolysis to provide oxygen and nutrients. Tumor hypoxia is a common characteristic of many solid tumors, and it essentially happens when the growth of the tumor exceeds the concomitant angiogenesis. Hypoxia-inducible factor 1 (HIF-1) as the critical transcription factor in hypoxia regulation is activated to adapt to this hypoxia situation. Flavonoids, widely distributed in plants, comprise many polyphenolic secondary metabolites, possessing broadspectrum pharmacological activities, including their potentiality as anticancer agents. Due to their low toxicity, intense efforts have been made for investigating natural flavonoids and their derivatives that can be used as HIF-1α inhibitors for cancer therapy during the past few decades. In this review, we sum up the findings concerning the inhibition of HIF-1α by natural flavonoids in the last few years and propose the idea of designing tumor vascular and glycolytic multi-target inhibitors with HIF-1α as one of the targets.

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Hypoxia-inducible factor 1, a master transcription factor of cellular hypoxic gene expression

Journal of Anesthesia ◽

10.1007/s005400200011 ◽

2002 ◽

Vol 16 (2) ◽

pp. 150-159 ◽

Cited By ~ 41

Author(s):

Kiichi Hirota

Keyword(s):

Gene Expression ◽

Transcription Factor ◽

Hypoxia Inducible Factor ◽

Hypoxia Inducible Factor 1

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Apatinib Inhibits Angiogenesis in Intrahepatic Cholangiocarcinoma by Regulating the Vascular Endothelial Growth Factor Receptor-2/Signal Transducer and Activator of Transcription Factor 3/Hypoxia Inducible Factor 1 Subunit Alpha Signaling Axis

Pharmacology ◽

10.1159/000514410 ◽

2021 ◽

pp. 1-11

Author(s):

Man-Ping Huang ◽

Shan-Zhi Gu ◽

Bin Huang ◽

Guo-Wen Li ◽

Zheng-Ping Xiong ◽

...

Keyword(s):

Vascular Endothelial Growth Factor ◽

Transcription Factor ◽

Growth Factor ◽

Intrahepatic Cholangiocarcinoma ◽

Hypoxia Inducible Factor ◽

Growth Factor Receptor ◽

Vascular Endothelial ◽

Signal Transducer ◽

Hypoxia Inducible Factor 1 ◽

Endothelial Growth Factor

Introduction: Intrahepatic cholangiocarcinoma (ICC), which is difficult to diagnose and is usually fatal due to its late clinical presentation and a lack of eﬀective treatment, has risen over the past decades but without much improvement in prognosis. Objective: The study aimed to investigate the role of apatinib that targets vascular endothelial growth factor receptor-2 (VEGFR2) in ICC. Methods: MTT assays, cell scratch assays, and tube formation assays were used to assess the effect of apatinib on human ICC cell line (HuCCT-1) and RBE cells proliferation, migration, and angiogenic capacity, respectively. Expression of vascular endothelial growth factor (VEGF), VEGFR2, signal transducer and activator of transcription factor 3 (STAT3), pSTAT3, and hypoxia inducible factor 1 subunit alpha (HIF-1α) pathway proteins was assessed using Western blotting and mRNA expression analysis in HuCCT-1 was performed using RT-qPCR assays. The pcDNA 3.1(-)-VEGFR2 and pcDNA 3.1(-)-HIF-1α were transfected into HuCCT-1 and RBE cells using Lipofectamine 2,000 to obtain overexpressed HuCCT-1 and RBE cells. Results: We found that apatinib-inhibited proliferation, migration, and angiogenesis of HuCCT-1 and RBE cells in vitro in a dose-dependent manner. We also proved that apatinib effectively inhibits angiogenesis in tumor cells by blocking the expression of VEGF and VEGFR2 in these cells. In addition, we demonstrated that apatinib regulates the expression of STAT3 phosphorylation by inhibiting VEGFR2. Finally, we showed that apatinib regulates ICC angiogenesis and HIF-1α/VEGF expression via STAT3. Conclusions: Based on the above findings, we conclude that apatinib inhibits HuCCT-1 and RBE cell proliferation, migration, and tumor angiogenesis by inhibiting the VEGFR2/STAT3/HIF-1α axis signaling pathway. Apatinib can be a promising drug for ICC-targeted molecular therapy.

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Hypoxia inducible factor down-regulation, cancer and cancer stem cells (CSCs): ongoing success stories

MedChemComm ◽

10.1039/c6md00432f ◽

2017 ◽

Vol 8 (1) ◽

pp. 21-52 ◽

Cited By ~ 8

Author(s):

Anthony R. Martin ◽

Cyril Ronco ◽

Luc Demange ◽

Rachid Benhida

Keyword(s):

Stem Cells ◽

Transcription Factor ◽

Cancer Stem Cells ◽

Hypoxia Inducible Factor ◽

Large Set ◽

Down Regulation ◽

Self Renewal ◽

Hypoxia Inducible Factor 1 ◽

Success Stories ◽

Tumour Vascularization

In cancers, hypoxia inducible factor 1 (HIF-1) is an over-expressed transcription factor, which regulates a large set of genes involved in tumour vascularization, metastases, and cancer stem cells (CSCs) formation and self-renewal.

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Abstract 1239: The transcription factor Kaiso negatively regulates the hypoxia inducible factor-1 alpha

10.1158/1538-7445.am10-1239 ◽

2010 ◽

Author(s):

Christina C. Pierre ◽

Laura C. Beatty ◽

Juliet M. Daniel

Keyword(s):

Transcription Factor ◽

Hypoxia Inducible Factor ◽

Hypoxia Inducible Factor 1

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Activation of Hypoxia-Inducible Factor-1 in the Rat Cerebral Cortex after Transient Global Ischemia: Potential Role of Insulin-Like Growth Factor-1

Journal of Neuroscience ◽

10.1523/jneurosci.22-20-08922.2002 ◽

2002 ◽

Vol 22 (20) ◽

pp. 8922-8931 ◽

Cited By ~ 165

Author(s):

Juan C. Chavez ◽

Joseph C. LaManna

Keyword(s):

Cerebral Cortex ◽

Growth Factor ◽

Potential Role ◽

Hypoxia Inducible Factor ◽

Global Ischemia ◽

Rat Cerebral Cortex ◽

Insulin Like Growth Factor ◽

Hypoxia Inducible Factor 1 ◽

Transient Global Ischemia

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Regulation of Transcription by Hypoxia Requires a Multiprotein Complex That Includes Hypoxia-Inducible Factor 1, an Adjacent Transcription Factor, and p300/CREB Binding Protein

Molecular and Cellular Biology ◽

10.1128/mcb.18.7.4089 ◽

1998 ◽

Vol 18 (7) ◽

pp. 4089-4096 ◽

Cited By ~ 186

Author(s):

Benjamin L. Ebert ◽

H. Franklin Bunn

Keyword(s):

Transcription Factor ◽

Transcription Factors ◽

Dna Binding ◽

Binding Proteins ◽

Binding Protein ◽

Hypoxia Inducible Factor ◽

Dna Binding Proteins ◽

Creb Binding Protein ◽

Multiprotein Complex ◽

Hypoxia Inducible Factor 1

ABSTRACT Molecular adaptation to hypoxia depends on the binding of hypoxia-inducible factor 1 (HIF-1) to cognate response elements in oxygen-regulated genes. In addition, adjacent sequences are required for hypoxia-inducible transcription. To investigate the mechanism of interaction between these cis-acting sequences, the multiprotein complex binding to the lactate dehydrogenase A (LDH-A) promoter was characterized. The involvement of HIF-1, CREB-1/ATF-1, and p300/CREB binding protein (CBP) was demonstrated by techniques documenting in vitro binding, in combination with transient transfections that test the in vivo functional importance of each protein. In both the LDH-A promoter and the erythropoietin 3′ enhancer, formation of multiprotein complexes was analyzed by using biotinylated probes encompassing functionally critical cis-acting sequences. Strong binding of p300/CBP required interactions with multiple DNA binding proteins. Thus, the necessity of transcription factor binding sites adjacent to a HIF-1 site for hypoxically inducible transcription may be due to the requirement of p300 to interact with multiple transcription factors for high-affinity binding and activation of transcription. Since it has been found to interact with a wide range of transcription factors, p300 is likely to play a similar role in other genes, mediating interactions between DNA binding proteins, thereby activating stimulus-specific and tissue-specific gene transcription.

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