title: Quercetin suppresses HeLa cell viability via AMPK-induced HSP70 and EGFR down-regulation.
abstract: 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.
authors.affiliation: Department of Anatomy, Korea University College of Medicine, Seongbuk-gu, Seoul 136-701, South Korea.
authors.forename: Jin Hee
authors.initials: JH
authors.lastname: Jung
authors.forename: Jeong Ok
authors.initials: JO
authors.lastname: Lee
authors.forename: Ji Hae
authors.initials: JH
authors.lastname: Kim
authors.forename: Soo Kyung
authors.initials: SK
authors.lastname: Lee
authors.forename: Ga Young
authors.initials: GY
authors.lastname: You
authors.forename: Sun Hwa
authors.initials: SH
authors.lastname: Park
authors.forename: Ji Man
authors.initials: JM
authors.lastname: Park
authors.forename: Eung-Kyun
authors.initials: EK
authors.lastname: Kim
authors.forename: Pann-Ghill
authors.initials: PG
authors.lastname: Suh
authors.forename: Jin Kyung
authors.initials: JK
authors.lastname: An
authors.forename: Hyeon Soo
authors.initials: HS
authors.lastname: Kim
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000187:drug effects* / Q000378:metabolism; D000103:Acetyl-CoA Carboxylase / Q000187:drug effects / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D053148:Caspase 3 / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D066246:ErbB Receptors / Q000187:drug effects* / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000187:drug effects* / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D010744:Phosphoric Monoester Hydrolases / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D050721:Proto-Oncogene Proteins c-cbl / Q000819:agonists / Q000378:metabolism; D011794:Quercetin / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D000975:Antioxidants; D018840:HSP70 Heat-Shock Proteins; D011794:Quercetin; D050721:Proto-Oncogene Proteins c-cbl; C512478:EGFR protein, human; D066246:ErbB Receptors; D055372:AMP-Activated Protein Kinases; D010744:Phosphoric Monoester Hydrolases; D053148:Caspase 3; C067419:CBL protein, human; D000103:Acetyl-CoA Carboxylase