Salicylate activates AMPK and synergizes with metformin to reduce the survival of prostate and lung cancer cells ex vivo through inhibition of de novo lipogenesis
| Autor: | Paola Muti, Gregory R. Steinberg, Bruce E. Kemp, Andrew J. O'Brien, Vanessa P. Houde, Linda Villani, Theodoros Tsakiridis, Giovanni Blandino, Sandra Galic, Lindsay A. Broadfield |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Male
Lung Neoplasms Sodium Salicylate AMP-Activated Protein Kinases Biochemistry chemistry.chemical_compound Mice AMP-activated protein kinase Mice Knockout Aspirin biology Anti-Inflammatory Agents Non-Steroidal mammalian target of rapamycin (mTOR) Drug Synergism Metformin Neoplasm Proteins Lipogenesis Female medicine.drug acetyl-CoA carboxylase (ACC) medicine.medical_specialty Cell Survival aspirin proliferation fatty acids Internal medicine Cell Line Tumor medicine Animals Humans Hypoglycemic Agents Protein kinase A Molecular Biology Sodium salicylate Fatty acid synthesis Binding Sites AMPK Prostatic Neoplasms cholesterol Cell Biology Fibroblasts Embryo Mammalian Enzyme Activation Endocrinology chemistry biology.protein Cancer research 3-hydroxy-3-methyl-glutaryl (HMG)-CoA reductase Acetyl-CoA Carboxylase |
| Popis: | Aspirin, the pro-drug of salicylate, is associated with reduced incidence of death from cancers of the colon, lung and prostate and is commonly prescribed in combination with metformin in individuals with type 2 diabetes. Salicylate activates the AMP-activated protein kinase (AMPK) by binding at the A-769662 drug binding site on the AMPK β1-subunit, a mechanism that is distinct from metformin which disrupts the adenylate charge of the cell. A hallmark of many cancers is high rates of fatty acid synthesis and AMPK inhibits this pathway through phosphorylation of acetyl-CoA carboxylase (ACC). It is currently unknown whether targeting the AMPK–ACC-lipogenic pathway using salicylate and/or metformin may be effective for inhibiting cancer cell survival. Salicylate suppresses clonogenic survival of prostate and lung cancer cells at therapeutic concentrations achievable following the ingestion of aspirin ( |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|