ArticleInternational journal of molecular sciences2021
Canagliflozin Modulates Hypoxia-Induced Metastasis, Angiogenesis and Glycolysis by Decreasing HIF-1α Protein Synthesis via AKT/mTOR Pathway.
Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 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
34 citing papers in PubMed, 56 citations in OpenAlex.
- Article
- From diabetes to tumor growth: unravelling the impact of glucose-lowering therapies.Endocrine · 2026Review
- Metabolic Concepts of Sodium-Glucose Cotransporter 2 Inhibitors-Based Therapies Against Hepatocarcinogenesis and Therapy Resistance in Hepatocellular Carcinoma.Life (Basel, Switzerland) · 2026Review
- Canagliflozin and Brusatol Synergize against LKB1-KEAP1 Co-Mutant NSCLC through AKT Suppression.International journal of biological sciences · 2026Article
- Progression and Metastasis of Lung Cancer: Clinical Features, Molecular Mechanisms, and Clinical Managements.MedComm · 2025Review
- Therapeutic efficacy of canagliflozin against hepatocarcinogenesis induced by CDD/DEN/TAA in a rat model: regulation of AMPK/HIF-1α/YAP-1/TAZ signaling pathways.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Long noncoding RNA RHPN1-AS1 promotes hepatocellular carcinoma progression under hypoxia through interaction with RPS15A protein.Medical oncology (Northwood, London, England) · 2025Article
- CLT-003 exerts anti-tumor activity in pancreatic cancer by blocking the PI3K/AKT/HIF-1α pathway.Cancer biology & medicine · 2025Article
- Chronic hepatitis B with type 2 diabetes mellitus: Association between glycemic control and liver fibrosis.World journal of diabetes · 2025Article
- Unveiling the anticancer potential of SGLT-2 inhibitors: mechanisms and prospects in clinical oncology-a narrative review.European journal of medical research · 2025Review
- Article
- Exploring the Role of SGLT2 Inhibitors in Cancer: Mechanisms of Action and Therapeutic Opportunities.Cancers · 2025Review
- Neutrophil extracellular traps in tumor metabolism and microenvironment.Biomarker research · 2025Review
- Advances in sodium-glucose transporter protein 2 inhibitors and tumors.Frontiers in oncology · 2025Review
- Metabolic reprogramming of glucose: the metabolic basis for the occurrence and development of hepatocellular carcinoma.Frontiers in oncology · 2025Review
- Multi-dimensional roles of sodium-glucose cotransporter 2 inhibitors: beyond hypoglycemic and cardiorenal protection.Frontiers in endocrinology · 2025Review
- Hypoxia upregulates hepatic angiopoietin-2 transcription to promote the progression of hepatocellular carcinoma.World journal of hepatology · 2024Article
- Anti-Diabetic Therapies and Cancer: From Bench to Bedside.Biomolecules · 2024Review
- Repositioning Canagliflozin for Mitigation of Aluminium Chloride-Induced Alzheimer's Disease: Involvement of TXNIP/NLRP3 Inflammasome Axis, Mitochondrial Dysfunction, and SIRT1/HMGB1 Signalling.Medicina (Kaunas, Lithuania) · 2024Article
- Glucose competition between endothelial cells in the blood-spinal cord barrier and infiltrating regulatory T cells is linked to sleep restriction-induced hyperalgesia.BMC medicine · 2024Article
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
The microenvironment plays a vital role in tumor progression, and hypoxia is a typical microenvironment feature in nearly all solid tumors. In this study, we focused on elucidating the effect of canagliflozin (CANA), a new class of antidiabetic agents, on hepatocarcinoma (HCC) tumorigenesis under hypoxia, and demonstrated that CANA could significantly inhibit hypoxia-induced metastasis, angiogenesis, and metabolic reprogramming in HCC. At the molecular level, this was accompanied by a reduction in VEGF expression level, as well as a reduction in the epithelial-to-mesenchymal transition (EMT)-related proteins and glycolysis-related proteins. Next, we focused our study particularly on the modulation of HIF-1α by CANA, which revealed that CANA decreased HIF-1α protein level by inhibiting its synthesis without affecting its proteasomal degradation. Furthermore, the AKT/mTOR pathway, which plays an important role in HIF-1α transcription and translation, was also inhibited by CANA. Thus, it can be concluded that CANA decreased metastasis, angiogenesis, and metabolic reprogramming in HCC by inhibiting HIF-1α protein accumulation, probably by targeting the AKT/mTOR pathway. Based on our results, we propose that CANA should be evaluated as a new treatment modality for liver cancer.
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