Quercetin suppresses HeLa cell viability via AMPK-induced HSP70 and EGFR down-regulation.
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.
Jung
Jin Hee
JH
Department of Anatomy, Korea University College of Medicine, Seongbuk-gu, Seoul 136-701, South Korea.
Lee
Jeong Ok
JO
Kim
Ji Hae
JH
Lee
Soo Kyung
SK
You
Ga Young
GY
Park
Sun Hwa
SH
Park
Ji Man
JM
Kim
Eung-Kyun
EK
Suh
Pann-Ghill
PG
An
Jin Kyung
JK
Kim
Hyeon Soo
HS
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
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