title: Apoptotic effect of EGCG in HT-29 colon cancer cells via AMPK signal pathway.
abstract: EGCG [(-)epigallocatechin-3-gallate], a green tea-derived polyphenol, has been shown to suppress cancer cell proliferation, and interfere with the several signaling pathways and induce apoptosis. Practically, there is emerging evidence that EGCG has a potential to increase the efficacy of chemotherapy in patients. We hypothesized that EGCG may exert cell cytotoxicity through modulating AMPK (AMP-activated protein kinase) followed by the decrease in COX-2 expression. EGCG treatment to colon cancer cells resulted in a strong activation of AMPK and an inhibition of COX-2 expression. The decreased COX-2 expression as well as prostaglandin E(2) secretion by EGCG was completely abolished by inhibiting AMPK by an AMPK inhibitor, Compound C. Also, the activation of AMPK was accompanied with the reduction of VEGF (vascular endothelial growth factor) and glucose transporter, Glut-1 in EGCG-treated cancer cells. These findings support the regulatory role of AMPK in COX-2 expression in EGCG-treated cancer cells. Furthermore, we have found that reactive oxygen species (ROS) is an upstream signal of AMPK, and the combined treatment of EGCG and chemotherapeutic agents, 5-FU or Etoposide, exert a novel therapeutic effect on chemo-resistant colon cancer cells. AMPK, a molecule of newly defined cancer target, was shown to control COX-2 in EGCG-treated colon cancer cells.
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical Research Center for Bioreaction to Reactive Oxygen Species, Kyung Hee University College of Medicine, Seoul, South Korea.
authors.forename: Jin-Taek
authors.initials: JT
authors.lastname: Hwang
authors.forename: Joohun
authors.initials: J
authors.lastname: Ha
authors.forename: In-Ja
authors.initials: IJ
authors.lastname: Park
authors.forename: Seong-Kyu
authors.initials: SK
authors.lastname: Lee
authors.forename: Haing Woon
authors.initials: HW
authors.lastname: Baik
authors.forename: Young Min
authors.initials: YM
authors.lastname: Kim
authors.forename: Ock Jin
authors.initials: OJ
authors.lastname: Park
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic; D019073:HT29 Cells; D006801:Humans; D008565:Membrane Proteins / Q000502:physiology*; D011494:Protein Kinases / Q000502:physiology*; D011720:Pyrazoles / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000032:analysis; D015398:Signal Transduction
chemical_list: D008565:Membrane Proteins; D011720:Pyrazoles; D011743:Pyrimidines; D017382:Reactive Oxygen Species; C516138:dorsomorphin; D002392:Catechin; C045651:epigallocatechin gallate; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011494:Protein Kinases; D000091162:AMP-Activated Protein Kinase Kinases