ArticleBritish journal of pharmacology2017
Curcuminoid EF24 enhances the anti-tumour activity of Akt inhibitor MK-2206 through ROS-mediated endoplasmic reticulum stress and mitochondrial dysfunction in gastric cancer.
Article in British journal of pharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 42 citations in OpenAlex.
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- Insights into the Mode of Action of Novel Morpholinated Curcumin Derivatives Exhibiting Potent Antitumor Activity in Bladder Cancer Cells In Vitro.Molecules (Basel, Switzerland) · 2025Article
- mTORC1-Driven Protein Translation Correlates with Clinical Benefit of Capivasertib within a Genetically Preselected Cohort of PIK3CA-Altered Tumors.Cancer research communications · 2024Article
- Mitochondria-associated endoplasmic reticulum membrane (MAM): a dark horse for diabetic cardiomyopathy treatment.Cell death discovery · 2024Review
- Harmine Hydrochloride Induces G2/M Cell Cycle Arrest and Apoptosis in SK-Hep1 Hepatocellular Carcinoma Cells by Regulating Mitogen-Activated Protein Kinases and the PI3K/AKT Pathway.Preventive nutrition and food science · 2023Article
- Induction of Hepatocellular Carcinoma Cell Cycle Arrest and Apoptosis byJournal of cancer prevention · 2023Article
- Review
- Development of a Signature Based on Eight Metastatic-Related Genes for Prognosis of GC Patients.Molecular biotechnology · 2023Article
- Lobetyolin inhibits cell proliferation and induces cell apoptosis by downregulating ASCT2 in gastric cancer.Cytotechnology · 2023Article
- Isoquercitrin Induces Endoplasmic Reticulum Stress and Immunogenic Cell Death in Gastric Cancer Cells.Biochemical genetics · 2023Article
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- Harmine Hydrochloride Triggers G2/M Cell Cycle Arrest and Apoptosis in HCT116 Cells through ERK and PI3K/AKT/mTOR Signaling Pathways.Preventive nutrition and food science · 2021Article
- Triclosan induces ROS-dependent cell death and autophagy in A375 melanoma cells.Oncology letters · 2020Article
- A Review of Research Progress in Multidrug-Resistance Mechanisms in Gastric Cancer.OncoTargets and therapy · 2020Review
- Ascorbic Acid Sensitizes Colorectal Carcinoma to the Cytotoxicity of Arsenic TrioxideFrontiers in pharmacology · 2020Article
- Chelerythrine induces apoptosis via ROS-mediated endoplasmic reticulum stress and STAT3 pathways in human renal cell carcinoma.Journal of cellular and molecular medicine · 2020Article
- The synergistic effects of oxaliplatin and piperlongumine on colorectal cancer are mediated by oxidative stress.Cell death & disease · 2019Article
- Article
- The Combination of MK-2206 and WZB117 Exerts a Synergistic Cytotoxic Effect Against Breast Cancer Cells.Frontiers in pharmacology · 2019Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeGastric cancer is one of the leading causes of morbidity and mortality worldwide. Akt is an anti-apoptotic kinase that plays a dynamic role in cell survival and is implicated in the pathogenesis of gastric cancer. MK-2206, the first allosteric inhibitor of Akt, is in clinical trials for a number of cancers. Although preclinical studies showed promise, clinical trials reported it had no effect when given alone at tolerated doses. The aim of our study was to delineate the effects of MK-2206 on gastric cancer cells and explore the ability of combination treatments to enhance the anti-tumour activity of MK-2206. EXPERIMENTAL APPROACH: SGC-7901, BGC-823 cells and immunodeficient mice were chosen as a model to study the treatment effects. Changes in cell viability, apoptosis and ROS, endoplasmic reticulum stress and mitochondrial dysfunction in the cells were analysed by MTT assays, ROS imaging and FACSCalibur, electron microscopy, JC-1 staining and western blotting. KEY
resultsMK-2206 induced apoptotic cell death through the generation of ROS. We utilized ROS production to target gastric cancer cells by combining MK-2206 and an ROS inducer EF24. Our in vitro and in vivo xenograft studies showed that combined treatment with MK-2206 and EF24 synergistically induced apoptosis in gastric cancer cells and caused cell cycle arrest. These activities were mediated through ROS generation and the induction of endoplasmic reticulum stress and mitochondrial dysfunction. CONCLUSION AND IMPLICATIONS: Targeting ROS generation by using a combination of an Akt inhibitor and EF24 could have potential as a therapy for gastric cancer.
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