ArticleMolecules and cells2015
The Histone Methyltransferase Inhibitor BIX01294 Inhibits HIF-1α Stability and Angiogenesis.
Article in Molecules and cells, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Targeting epigenetics and non-coding RNAs in atherosclerosis: from mechanisms to therapeutics.Pharmacology & therapeutics · 2019Pooled it
- HIF-1α signaling: Essential roles in tumorigenesis and implications in targeted therapies.Genes & diseases · 2024Review
- Mechanisms of HIF-driven immunosuppression in tumour microenvironment.Journal of the Egyptian National Cancer Institute · 2023Review
- Mechanisms shared between cancer, heart failure, and targeted anti-cancer therapies.Cardiovascular research · 2023Review
- Exploring the natural products chemical space through a molecular search to discover potential inhibitors that target the hypoxia-inducible factor (HIF) prolyl hydroxylase domain (PHD).Frontiers in pharmacology · 2023Article
- Article
- Histone Methyltransferase G9a-Promoted Progression of Hepatocellular Carcinoma Is Targeted by Liver-Specific Hsa-miR-122.Cancers · 2021Article
- Ways into Understanding HIF Inhibition.Cancers · 2021Review
- Histone Methylation: Achilles Heel and Powerful Mediator of Periodontal Homeostasis.Journal of dental research · 2020Article
- Epigenetic crosstalk between hypoxia and tumor driven by HIF regulation.Journal of experimental & clinical cancer research : CR · 2020Review
- Histone methylation and vascular biology.Clinical epigenetics · 2020Review
- G9a Suppression Alleviates Corneal Neovascularization through Blocking Nox4-Mediated Oxidative Stress.Oxidative medicine and cellular longevity · 2020Article
- Glucometabolic Reprogramming in the Hepatocellular Carcinoma Microenvironment: Cause and Effect.Cancer management and research · 2020Review
- The transcriptional factors HIF-1 and HIF-2 and their novel inhibitors in cancer therapy.Expert opinion on drug discovery · 2019Review
- BIX-01294 sensitizes renal cancer Caki cells to TRAIL-induced apoptosis through downregulation of survivin expression and upregulation of DR5 expression.Cell death discovery · 2018Article
- Review
- Epigenetic regulators: multifunctional proteins modulating hypoxia-inducible factor-α protein stability and activity.Cellular and molecular life sciences : CMLS · 2018Review
- Out of sight, out of mind? Germ cells and the potential impacts of epigenomic drugs.F1000Research · 2018Review
- [Methyltransferase inhibitor BIX01294 promotes the migration and inhibits decidualization of mouse uterine stromal cells in vitro].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2017Article
- The expanding role of the Ehmt2/G9a complex in neurodevelopment.Neurogenesis (Austin, Tex.) · 2017Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hypoxia-inducible factor (HIF) is a key regulator of tumor growth and angiogenesis. Recent studies have shown that, BIX01294, a G9a histone methyltransferase (HMT)-specific inhibitor, induces apoptosis and inhibits the proliferation, migration, and invasion of cancer cells. However, not many studies have investigated whether inhibition of G9a HMT can modulate HIF-1α stability and angiogenesis. Here, we show that BIX01294 dose-dependently decreases levels of HIF-1α in HepG2 human hepatocellular carcinoma cells. The half-life of HIF-1α, expression of proline hydroxylase 2 (PHD2), hydroxylated HIF-1α and von Hippel-Lindau protein (pVHL) under hypoxic conditions were decreased by BIX01294. The mRNA expression and secretion of vascular endothelial growth factor (VEGF) were also significantly reduced by BIX01294 under hypoxic conditions in HepG2 cells. BIX01294 remarkably decreased angiogenic activity induced by VEGF in vitro, ex vivo, and in vivo, as demonstrated by assays using human umbilical vein endothelial cells (HUVECs), mouse aortic rings, and chick chorioallantoic membranes (CAMs), respectively. Furthermore, BIX01294 suppressed VEGF-induced matrix metalloproteinase 2 (MMP2) activity and inhibited VEGF-induced phosphorylation of VEGF receptor 2 (VEGFR-2), focal adhesion kinase (FAK), and paxillin in HUVECs. In addition, BIX01294 inhibited VEGF-induced formation of actin cytoskeletal stress fibers. In conclusion, we demonstrated that BIX01294 inhibits HIF-1α stability and VEGF-induced angiogenesis through the VEGFR-2 signaling pathway and actin cytoskeletal remodeling, indicating a promising approach for developing novel therapeutics to stop tumor progression.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.