ArticleScientific reports2015
The multikinase inhibitor Sorafenib enhances glycolysis and synergizes with glycolysis blockade for cancer cell killing.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 75 citations in OpenAlex.
- Metabolic Switch in Hepatocellular Carcinoma Patients Treated with Sorafenib: a Proof-of-Concept Trial.Molecular imaging and biology · 2020Trial
- Article
- SLC16A3 as an immunosuppressive Kupffer cell marker predicts poor prognosis in HBV-positive hepatocellular carcinoma.Journal of translational medicine · 2025Article
- Salsalate improves the anti-tumor efficacy of lenvatinib in MASH-driven hepatocellular carcinoma.JHEP reports : innovation in hepatology · 2025Article
- Research Progress of Liver Cancer Recurrence Based on Energy Metabolism of Liver Cancer Stem Cells.Journal of hepatocellular carcinoma · 2025Review
- Crippled Hepatocarcinogenesis Inhibition of Quercetin in Glycolysis Pathway with Hepatic Farnesoid X Receptor Deficiency.Current pharmaceutical design · 2025Article
- Mitochondrial metabolism: A moving target in hepatocellular carcinoma therapy.Journal of cellular physiology · 2025Review
- Role of mitophagy in breast cancer: mitophagy-apoptosis balance and reactive oxygen species play determining role.Frontiers in physiology · 2025Review
- SLC50A1 inhibits the doxorubicin sensitivity in hepatocellular carcinoma cells through regulating the tumor glycolysis.Cell death discovery · 2024Article
- Targeted regulation of autophagy using sorafenib-loaded biomineralization nanoenzyme for enhanced photodynamic therapy of hepatoma.Materials today. Bio · 2024Article
- Review
- Article
- Broad Transcriptomic Impact of Sorafenib and Its Relation to the Antitumoral Properties in Liver Cancer Cells.Cancers · 2022Article
- Antiangiogenic Drugs in NASH: Evidence of a Possible New Therapeutic Approach.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Antioxidants Threaten Multikinase Inhibitor Efficacy against Liver Cancer by Blocking Mitochondrial Reactive Oxygen Species.Antioxidants (Basel, Switzerland) · 2021Article
- USP29-mediated HIF1α stabilization is associated with Sorafenib resistance of hepatocellular carcinoma cells by upregulating glycolysis.Oncogenesis · 2021Article
- Review
- Development of an Aerobic Glycolysis Index for Predicting the Sorafenib Sensitivity and Prognosis of Hepatocellular Carcinoma.Frontiers in oncology · 2021Article
- Establishment of an Immunocompetent Metastasis Rat Model with Hepatocyte Cancer Stem Cells.Cancers · 2020Article
- Can a metabolism-targeted therapeutic intervention successfully subjugate SARS-COV-2? A scientific rational.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2020Review
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although the only effective drug against primary hepatocarcinoma, the multikinase inhibitor Sorafenib (SFB) usually fails to eradicate liver cancer. Since SFB targets mitochondria, cell metabolic reprogramming may underlie intrinsic tumor resistance. To characterize cancer cell metabolic response to SFB, we measured oxygen consumption, generation of reactive oxygen species (ROS) and ATP content in rat LCSC (Liver Cancer Stem Cells) -2 cells exposed to the drug. Genome wide analysis of gene expression was performed by Affymetrix technology. SFB cytotoxicity was evaluated by multiple assays in the presence or absence of metabolic inhibitors, or in cells genetically depleted of mitochondria. We found that low concentrations (2.5-5 μM) of SFB had a relatively modest effect on LCSC-2 or 293 T cell growth, but damaged mitochondria and increased intracellular ROS. Gene expression profiling of SFB-treated cells was consistent with a shift toward aerobic glycolysis and, accordingly, SFB cytotoxicity was dramatically increased by glucose withdrawal or the glycolytic inhibitor 2-DG. Under metabolic stress, activation of the AMP dependent Protein Kinase (AMPK), but not ROS blockade, protected cells from death. We conclude that mitochondrial damage and ROS drive cell killing by SFB, while glycolytic cell reprogramming may represent a resistance strategy potentially targetable by combination therapies.
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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.