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

AMPK, AMP-activated protein kinase; COX-2, cyclooxygenase-2 AMPK (AMP-activated protein kinase) is highly con-served in eukaryotes, where it functions primarily as a sensor of cellular energy status. Recent studies in-dicate 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 re-lated to a decrease in COX-2 expression. The applica-tion 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 ef-fects of quercetin. The suppressive or growth in-hibitory effects of quercetin on COX-2 were abolished by treating cancer cells with an AMPK inhibitor Compound C. These results suggest that AMPK is cru-cial to the anti-cancer effect of quercetin and that the AMPK-COX-2 signaling pathway is important in quer-cetin-mediated cancer control