ArticleCellular & molecular biology letters2024
SGLT2 inhibitor promotes mitochondrial dysfunction and ER-phagy in colorectal cancer cells.
Article in Cellular & molecular biology letters, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Sotagliflozin, a Dual SGLT1/2 Inhibitor, Modulates DNMT1 and Class I/II HDAC Expression in Association With Anticancer Effects in Breast and Lung Cancer Cells.Cell biology international · 2026Article
- SGLT2 inhibition induces autophagic flux blockade and sensitizes pancreatic cancer to EGFR-targeted therapy.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- Relationships of SGLT2 inhibition, circulating metabolites, and cancer: A Mendelian randomization study.Medicine · 2026Article
- Role of Ki-67 and Annexin V in the Biological Behavior of Salivary Gland Tumors: Insights into Proliferation and Apoptosis.Current issues in molecular biology · 2026Article
- In vitro evidence and integrative bioinformatics identify the SGLT2-PPARγ axis as a target against polyethylene microplastic-driven metabolic reprogramming in colorectal cancer cells.Journal of translational medicine · 2026Article
- The SGLT2 inhibitor empagliflozin promotes increased fatty acid oxidation in skeletal muscle cells.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Role of SIRT3 in digestive system diseases and therapeutic prospects (Review).International journal of molecular medicine · 2026Review
- Pharmacological mechanisms and clinical impacts of antidiabetic drugs on colorectal cancer risk: a systematic review.Frontiers in pharmacology · 2026Review
- Sodium-Glucose Cotransporter 2 Inhibitors as Emerging Anticancer Agents.Diabetes & metabolism journal · 2026Review
- Beyond the Cardio-Renal-Metabolic Axis: Emerging Therapeutic Targets and Novel Mechanisms of Action of Flozins.Journal of clinical medicine · 2025Review
- Association of sodium-glucose cotransporter-2 inhibitor use and mortality in patients with endometrial cancer: a retrospective cohort study.BMC cancer · 2025Article
- Article
- Molecular mechanisms and computational insights into human SGLTs: advancing toward selective SGLT1 inhibition.Frontiers in molecular biosciences · 2025Review
- SGLT2 Inhibitors in Combination Therapies for Tumors: A Novel Approach to Synergistic Treatment Strategies.Drug design, development and therapy · 2025Review
- The protective effect of sodium-glucose cotransporter 2 inhibitors and the incidence of ovarian cancer: a nationwide cohort preliminary study.Archives of medical science : AMS · 2025Article
- Anti-Diabetic Therapies and Cancer: From Bench to Bedside.Biomolecules · 2024Review
- Obesity-Associated Colorectal Cancer.International journal of molecular sciences · 2024Review
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Authors and funding
9 authors.
Funding
Abstract
backgroundSodium-glucose transporter 2 (SGLT2) inhibitors (iSGLT2) are approved medications for type 2 diabetes. Recent studies indicate that iSGLT2 inhibit the growth of some cancer cells. However, the mechanism(s) remains to be fully elucidated.
methodsThe SGLT2 levels were determined in normal colon CCD 841 CoN and, HCT 116, HT-29, SW480 and LoVo colorectal cancer (CRC) cell lines by quantitative real-time PCR and western blot. The effect of iSGLT2 canagliflozin on cell proliferation was examined using CCK-8, as its role on CRC cells metabolism and tumorigenesis has been evaluated by XF HS Seahorse Bioanalyzer and flow cytometric analyses. Transient gene silencing experiments and analysis of protein-protein interaction network were conducted to evaluate the SGLT2 molecular targets in CRC cells.
resultsData showed that the treatment with iSGLT2 (50 µM) for 72 h induced cell cycle arrest (p < 0.001), impaired glucose and energetic metabolism (p < 0.001), promoted apoptotic cell death and ER stress flowing into autophagy (p < 0.001) in HCT 116 and HT-29 cells. These cellular events were accompanied by sirtuin 3 (SIRT3) upregulation (p < 0.01), as also supported by SIRT3 transient silencing experiments resulting in the attenuation of the effects of iSGLT2 on the cellular metabolic/energetic alterations and the induction of programmed cell death. The identification and validation of dipeptidyl peptidase 4 (DPP4) as potential common target of SGLT2 and SIRT3 were also assessed.
conclusionsThese results deepened knowledge on the iSGLT2 contribution in limiting CRC tumorigenesis unveiling the SGLT2/SIRT3 axis in the cytotoxic mechanisms.
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