title: Coffee phenolic phytochemicals suppress colon cancer metastasis by targeting MEK and TOPK.
abstract: Epidemiological studies suggest that coffee consumption reduces the risk of cancers, including colon cancer, but the molecular mechanisms and target(s) underlying the chemopreventive effects of coffee and its active ingredient(s) remain unknown. Based on serving size or daily units, coffee contains larger amounts of phenolic phytochemicals than tea or red wine. Coffee or chlorogenic acid inhibited CT-26 colon cancer cell-induced lung metastasis by blocking phosphorylation of ERKs. Coffee or caffeic acid (CaA) strongly suppressed mitogen-activated MEK1 and TOPK activities and bound directly to either MEK1 or TOPK in an ATP-noncompetitive manner. Coffee or CaA, but not caffeine, inhibited ERKs phosphorylation, AP-1 and NF-κB transactivation and subsequently inhibited TPA-, EGF- and H-Ras-induced neoplastic transformation of JB6 P+ cells. Coffee consumption was also associated with a significant attenuation of ERKs phosphorylation in colon cancer patients. These results suggest that coffee and CaA target MEK1 and TOPK to suppress colon cancer metastasis and neoplastic cell transformation.
authors.affiliation: The Hormel Institute, University of Minnesota, Austin, MN 55912, USA.
authors.forename: Nam Joo
authors.initials: NJ
authors.lastname: Kang
authors.forename: Ki Won
authors.initials: KW
authors.lastname: Lee
authors.forename: Bo Hyun
authors.initials: BH
authors.lastname: Kim
authors.forename: Ann M
authors.initials: AM
authors.lastname: Bode
authors.forename: Hyo-Jeong
authors.initials: HJ
authors.lastname: Lee
authors.forename: Yong-Seok
authors.initials: YS
authors.lastname: Heo
authors.forename: Lisa
authors.initials: L
authors.lastname: Boardman
authors.forename: Paul
authors.initials: P
authors.lastname: Limburg
authors.forename: Hyong Joo
authors.initials: HJ
authors.lastname: Lee
authors.forename: Zigang
authors.initials: Z
authors.lastname: Dong
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D002726:Chlorogenic Acid / Q000627:therapeutic use; D003069:Coffee; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D006801:Humans; D007124:Immunoenzyme Techniques; D008156:Luciferases / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism / Q000517:prevention & control* / Q000556:secondary; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D020929:Mitogen-Activated Protein Kinase Kinases / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D010636:Phenols / Q000627:therapeutic use*; D011446:Prospective Studies; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D003069:Coffee; D010636:Phenols; D002726:Chlorogenic Acid; D008156:Luciferases; D017346:Protein Serine-Threonine Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; C409022:PDZ-binding kinase; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9