AMP kinase/cyclooxygenase-2 pathway regulates proliferation and apoptosis of cancer cells treated with quercetin.
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.
Lee
Yun Kyoung
YK
Department of Food and Nutrition, Hannam University Daedeok Valley Campus, Daejeon 305-811, Korea.
Park
Song Yi
SY
Kim
Young Min
YM
Lee
Won Sup
WS
Park
Ock Jin
OJ
D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000502:physiology*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D004789:Enzyme Activation; D006801:Humans; D011720:Pyrazoles / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D011794:Quercetin / Q000494:pharmacology*
D016588:Anticarcinogenic Agents; D000975:Antioxidants; D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines; C516138:dorsomorphin; D011794:Quercetin; D051546:Cyclooxygenase 2; D055372:AMP-Activated Protein Kinases