Exp Mol Med.  2009 Mar;41(3):201-207. 10.3858/emm.2009.41.3.023.

AMP kinase/cyclooxygenase-2 pathway regulates proliferation and apoptosis of cancer cells treated with quercetin

• Lee YK
• Park SY
• Kim YM
• Lee WS
• Park OJ

• KMID: 1123467
• DOI: http://doi.org/10.3858/emm.2009.41.3.023

Abstract

AMPK (AMP-activated protein kinase) is highly conserved in eukaryotes, where it functions primarily as a sensor of cellular energy status. Recent studies indicate that AMPK activation strongly suppresses cell proliferation in non-malignant cells as well as in tumor cells. In this study, quercetin activated AMPK in MCF breast cancer cell lines and HT-29 colon cancer cells, and this activation of AMPK seemed to be closely related to a decrease in COX-2 expression. The application of a COX-2 inhibitor or cox-2(-/-) cells supported the idea that AMPK is an upstream signal of COX-2, and is required for the anti-proliferatory and pro-apoptotic effects of quercetin. The suppressive or growth inhibitory effects of quercetin on COX-2 were abolished by treating cancer cells with an AMPK inhibitor Compound C. These results suggest that AMPK is crucial to the anti-cancer effect of quercetin and that the AMPK-COX-2 signaling pathway is important in quercetin-mediated cancer control.

Keyword

AMP-activated protein kinases; apoptosis; cyclooxygenase-2; growth inhibitors; HT-29 cells; quercetin

MeSH Terms

AMP-Activated Protein Kinases/antagonists & inhibitors/*physiology
Anticarcinogenic Agents/*pharmacology
Antioxidants/*pharmacology
Apoptosis/*drug effects
Cell Cycle/drug effects/physiology
Cell Line, Tumor
Cell Proliferation/*drug effects
Cyclooxygenase 2/genetics/*physiology
Cyclooxygenase 2 Inhibitors/pharmacology
Enzyme Activation
Humans
Pyrazoles/pharmacology
Pyrimidines/pharmacology
Quercetin/*pharmacology