Experimental & Molecular Medicine  2009;41(3):201-207

doi:10.3858/emm.2009.41.3.023

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

Yun Kyoung LEE 1 ; Song Yi PARK ; Young Min KIM ; Won Sup LEE ; Ock Jin PARK

Affiliations

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Keywords

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

Country

Republic of Korea

Language

English

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.