ArticleFrontiers in pharmacology2019
The Combination of MK-2206 and WZB117 Exerts a Synergistic Cytotoxic Effect Against Breast Cancer Cells.
Article in Frontiers in pharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 43 citations in OpenAlex.
- Concurrent Inhibition of AKT and GLUT1 Reveals Endpoint-Specific Effects on Glucose Metabolism and Cell Death in HepG2 Hepatocyte-Derived Cells.Biomedicines · 2026Article
- Targeting GLUTs in Cancer: Mechanisms, Combination Strategies, and Translational Challenges.Current medical science · 2026Review
- Research progress and therapeutic strategies in hepatocellular carcinoma metabolic reprogramming.Journal of advanced research · 2026Review
- Metabolic drivers of genome instability in cancer: mechanisms and therapeutic opportunities.Experimental hematology & oncology · 2026Review
- Emerging Targeted and Multimodal Therapeutic Strategies in Breast Cancer: A Comprehensive Review.Breast cancer (Dove Medical Press) · 2026Review
- A novel pan class-I glucose transporter inhibitor DRB18 exhibits synergistic effects with paclitaxelbioRxiv : the preprint server for biology · 2025Article
- Enhancing Chemotherapeutic Efficacy in Lung Cancer Cells Through Synergistic Targeting of the PI3K/AKT Pathway with Small Molecule Inhibitors.International journal of molecular sciences · 2025Article
- Treatment strategies targeting the phosphoinositide 3-kinase/protein kinase B/mechanistic target of rapamycin pathway against triple-negative breast cancer.World journal of clinical oncology · 2025Review
- Multifaced Anticancer Potential of Doxorubicin: Spotlight on Breast Cancer.Diseases & research · 2025Article
- Energy metabolism in health and diseases.Signal transduction and targeted therapy · 2025Review
- Impact of glycolysis enzymes and metabolites in regulating DNA damage repair in tumorigenesis and therapy.Cell communication and signaling : CCS · 2025Review
- Targeting Glucose Transporter 1 (GLUT1) in Cancer: Molecular Mechanisms and Nanomedicine Applications.International journal of nanomedicine · 2025Review
- Lactate-mediated metabolic reprogramming of tumor-associated macrophages: implications for tumor progression and therapeutic potential.Frontiers in immunology · 2025Review
- Article
- Boolean modeling of breast cancer signaling pathways uncovers mechanisms of drug synergy.PloS one · 2024Article
- Metabolic Phenotype Intricacies on Altered Glucose Metabolism of Breast Cancer Cells upon Glut-1 Inhibition and Mimic Hypoxia In Vitro.Applied biochemistry and biotechnology · 2023Article
- Deciphering the Mysterious Relationship between the Cross-Pathogenetic Mechanisms of Neurodegenerative and Oncological Diseases.International journal of molecular sciences · 2023Review
- Modulating Glycolysis to Improve Cancer Therapy.International journal of molecular sciences · 2023Review
- Discovery of New Glucose Uptake Inhibitors as Potential Anticancer Agents by Non-Radioactive Cell-Based Assays.Molecules (Basel, Switzerland) · 2022Article
- Targeting Energy Metabolism in Cancer Treatment.International journal of molecular sciences · 2022Review
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
Breast cancer is the most commonly diagnosed cancer and the second leading cause of cancer death in women. Hormone receptor-positive breast cancer is usually subjected to hormone therapy, while triple-negative breast cancer is more formidable and poses a therapeutic challenge. Glucose transporters are potential targets for the development of anticancer drugs. In search of anticancer agents whose effect could be enhanced by a GLUT1 inhibitor WZB117, we found that MK-2206, a potent allosteric Akt inhibitor, when combined with WZB117, showed a synergistic effect on growth inhibition and apoptosis induction in breast cancer cells, including ER(+) MCF-7 cells and triple-negative MDA-MB-231 cells. The combination index values at 50% growth inhibition were 0.45 and 0.21, respectively. Mechanism studies revealed that MK-2206 and WZB117 exert a synergistic cytotoxic effect in both MCF-7 and MDA-MB-231 breast cancer cells by inhibiting Akt phosphorylation and inducing DNA damage. The combination may also compromise DNA damage repair and ultimately lead to apoptosis. Our findings suggest that the combination of Akt inhibitors and GLUT1 inhibitors could be a novel strategy to combat breast cancer.
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Registered trials
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.