Quercetin suppresses HeLa cell viability via AMPK-induced HSP70 and EGFR down-regulation
| Autor: | Jeong Ok Lee, Sun Hwa Park, Eung-Kyun Kim, Jin Hee Jung, Ji Man Park, Soo Kyung Lee, Ji Hae Kim, Pann-Ghill Suh, Jin Kyung An, Hyeon Soo Kim, Ga Young You |
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| Rok vydání: | 2010 |
| Předmět: |
Physiology
Cell Survival Clinical Biochemistry Down-Regulation Caspase 3 Apoptosis AMP-Activated Protein Kinases Antioxidants HeLa chemistry.chemical_compound AMP-activated protein kinase Neoplasms Humans heterocyclic compounds HSP70 Heat-Shock Proteins Viability assay Proto-Oncogene Proteins c-cbl Phosphorylation Protein kinase A biology AMPK Tyrosine phosphorylation Cell Biology biology.organism_classification Antineoplastic Agents Phytogenic Phosphoric Monoester Hydrolases ErbB Receptors chemistry biology.protein Cancer research Quercetin Acetyl-CoA Carboxylase HeLa Cells |
| Zdroj: | Journal of cellular physiology. 223(2) |
| ISSN: | 1097-4652 |
| Popis: | Quercetin, an anti-oxidant flavonoid that is widely distributed in the plant kingdom, has been suggested to have chemopreventive effects on cancer cells, although the mechanism is not completely understood. In this study, we found that quercetin increased the phosphorylation of AMP-activated protein kinase (AMPK) and downstream acetyl-CoA carboxylase (ACC) and suppressed the viability of HeLa cells. AICAR, an AMPK activator, and quercetin down-regulated heat shock protein (HSP)70 and increased the activity of the pro-apoptotic effector, caspase 3. Knock-down of AMPK blocked quercetin-mediated HSP70 down-regulation. Moreover, knock-down of HSP70 enhanced quercetin-mediated caspase 3 activation. Furthermore, quercetin sustained epidermal growth factor receptor (EGFR) activation by suppressing the phosphatases, PP2a and SHP-2. Finally, quercetin increased the interaction between EGFR and Cbl, and also induced the tyrosine phosphorylation of Cbl. Together, these results suggest that quercetin may have anti-tumor effects on HeLa cells via AMPK-induced HSP70 and down-regulation of EGFR. |
| Databáze: | OpenAIRE |
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