Quercetin suppresses HeLa cell viability via AMPK-induced HSP70 and EGFR down-regulation

• Published in: Journal of cellular physiology 2010-05, Vol.223 (2), p.408-414
• Main Authors: Jung, Jin Hee, Lee, Jeong Ok, Kim, Ji Hae, Lee, Soo Kyung, You, Ga Young, Park, Sun Hwa, Park, Ji Man, Kim, Eung-Kyun, Suh, Pann-Ghill, An, Jin Kyung, Kim, Hyeon Soo
• Format: Article
• Language: English
• Subjects: Acetyl-CoA Carboxylase - drug effects; Acetyl-CoA Carboxylase - metabolism; AMP-Activated Protein Kinases - drug effects; AMP-Activated Protein Kinases - metabolism; Antineoplastic Agents, Phytogenic - pharmacology; Antineoplastic Agents, Phytogenic - therapeutic use; Antioxidants - pharmacology; Antioxidants - therapeutic use; Apoptosis - drug effects; Apoptosis - physiology; Caspase 3 - drug effects; Caspase 3 - metabolism; Cell Survival - drug effects; Cell Survival - physiology; Down-Regulation - drug effects; Down-Regulation - physiology; HeLa Cells; HSP70 Heat-Shock Proteins - drug effects; HSP70 Heat-Shock Proteins - metabolism; Humans; Neoplasms - drug therapy; Neoplasms - metabolism; Neoplasms - physiopathology; Phosphoric Monoester Hydrolases - antagonists & inhibitors; Phosphoric Monoester Hydrolases - metabolism; Phosphorylation - drug effects; Proto-Oncogene Proteins c-cbl - agonists; Proto-Oncogene Proteins c-cbl - metabolism; Quercetin - pharmacology; Quercetin - therapeutic use; Receptor, Epidermal Growth Factor - drug effects; Receptor, Epidermal Growth Factor - metabolism
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.22049

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. J. Cell. Physiol. 223: 408–414, 2010. © 2010 Wiley‐Liss, Inc.