ArticleThe Journal of biological chemistry2011
Aldose reductase inhibition prevents hypoxia-induced increase in hypoxia-inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) by regulating 26 S proteasome-mediated protein degradation in human colon cancer cells.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 26 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
26 citing papers in PubMed, 38 citations in OpenAlex.
- The role of hypoxia-inducible factor-1α on colon cancer progression and metastasis.International journal of clinical oncology · 2025Review
- A One Stone Three Birds Paradigm of Photon-Driven Pyroptosis Dye for Amplifying Tumor Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Aldose Reductase: A Promising Therapeutic Target for High-Altitude Pulmonary Edema.International journal of molecular sciences · 2025Article
- RNA-seq analysis of blood from cave- and surface-dwellingFrontiers in physiology · 2025Article
- Fructose Metabolism in Cancer: Molecular Mechanisms and Therapeutic Implications.International journal of medical sciences · 2025Review
- Aldo-keto reductases: Role in cancer development and theranostics.Oncology research · 2024Review
- Endogenous Fructose Production and Metabolism Drive Metabolic Dysregulation and Liver Disease in Mice with Hereditary Fructose Intolerance.Nutrients · 2023Article
- AKR1B10 Inhibitor Epalrestat Facilitates Sorafenib-Induced Apoptosis and Autophagy Via Targeting the mTOR Pathway in Hepatocellular Carcinoma.International journal of medical sciences · 2020Article
- Article
- Aldose reductase inhibitor, fidarestat prevents doxorubicin-induced endothelial cell death and dysfunction.Biochemical pharmacology · 2018Article
- Aldose Reductase Inhibitor, Fidarestat Prevents High-fat Diet-induced Intestinal Polyps in ApcCurrent cancer drug targets · 2018Article
- Aldose reductase inhibitor increases doxorubicin-sensitivity of colon cancer cells and decreases cardiotoxicity.Scientific reports · 2017Article
- Protective role of fructokinase blockade in the pathogenesis of acute kidney injury in mice.Nature communications · 2017Article
- Shexiang Baoxin Pills for Coronary Heart Disease in Animal Models: Preclinical Evidence and Promoting Angiogenesis Mechanism.Frontiers in pharmacology · 2017Review
- Aldose Reductase Inhibitor Protects against Hyperglycemic Stress by Activating Nrf2-Dependent Antioxidant Proteins.Journal of diabetes research · 2017Article
- Gedunin abrogates aldose reductase, PI3K/Akt/mToR, and NF-κB signaling pathways to inhibit angiogenesis in a hamster model of oral carcinogenesis.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Global profiling of metabolic adaptation to hypoxic stress in human glioblastoma cells.PloS one · 2015Article
- Aldose reductase inhibition suppresses azoxymethane-induced colonic premalignant lesions in C57BL/KsJ-db/db mice.Cancer letters · 2014Article
- 4-Hydroxynonenal in the pathogenesis and progression of human diseases.Current medicinal chemistry · 2014Review
- Aldose reductase inhibition enhances TRAIL-induced human colon cancer cell apoptosis through AKT/FOXO3a-dependent upregulation of death receptors.Free radical biology & medicine · 2013Article
Corrections and comments
- Expression of concern · 2019-02-01Concerns/Issues about Data · Concerns/Issues about Results and/or Conclusions ·
- Expression of concern
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The development of intratumoral hypoxia, a hallmark of rapidly progressing solid tumors, renders tumor cells resistant to chemotherapy and radiation therapy. We have recently shown that inhibition of aldose reductase (AR), an enzyme that catalyzes the reduction of lipid aldehydes and their glutathione conjugates, prevents human colon cancer cell growth in culture as well as in nude mouse xenografts by inhibiting the NF-κB-dependent activation of oxidative stress-mediated inflammatory and carcinogenic markers. However, the role of AR in mediating hypoxic stress signals is not known. We therefore investigated the molecular mechanisms by which AR inhibition prevents the hypoxia-induced human colon cancer cells growth and invasion. Our results indicate that AR inhibition by the pharmacological inhibitor fidarestat or ablation by AR-specific siRNA prevents hypoxia-induced proliferation of HT29, SW480, and Caco-2 colon cancer cells. Furthermore, hypoxia-induced increase in the level of HIF-1α in colon cancer cells was significantly decreased by AR inhibition. During hypoxic conditions, treatment of HT29 cells with the AR inhibitor fidarestat significantly decreased the expression of vascular endothelial growth factor, a down target of HIF-1α, at both mRNA and protein levels and also prevented the activation of PI3K/AKT, GSK3β, Snail, and lysyl oxidase. Furthermore, inhibition of hypoxia-induced HIF-1α protein accumulation by AR inhibition was abolished in the presence of MG132, a potent inhibitor of the 26 S proteasome. In addition, AR inhibition also prevented the hypoxia-induced inflammatory molecules such as Cox-2 and PGE2 and expression of extracellular matrix proteins such as MMP2, vimentin, uPAR, and lysyl oxidase 2. In conclusion, our results indicate that AR mediates hypoxic signals, leading to tumor progression and invasion.
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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.