title: Implication of Akt, ERK1/2 and alternative p38MAPK signalling pathways in human colon cancer cell apoptosis induced by green tea EGCG.
abstract: We investigated apoptosis induced by the green tea component the epigallocatechin-3-gallate (EGCG) and the pathways underlying its activity in a colon cancer cell line. A complete understanding of the mechanism(s) and molecules targeted by green tea polyphenols could be useful in developing novel therapeutic approaches for cancer treatment. EGCG, which is the major polyphenol in green tea, has cytotoxic effects and induced cell death in HT-29 cell death. In this study, we evaluated the effect EGCG on mitogen-activated protein kinase (MAPK) and Akt pathways. EGCG treatment increased phospho-ERK1/2, -JNK1/2 and -p38α, -p38γ and -p38δ, as well as phospho-Akt levels. Using a combination of kinase inhibitors, we found that EGCG-induced cell death is partially blocked by inhibiting Akt, ERK1/2 or alternative p38MAPK activity. Our data suggest that these kinase pathways are involved in the anti-cancer effects of EGCG and indicate potential use of this compound as chemotherapeutic agent for colon cancer treatment.
authors: Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, Campus de Cantoblanco, 28049 Madrid, Spain; Department of Biochemistry and Molecular Biology, Facultad de Ciencias, Universidad de Extremadura, Avda, de Elvas s/n, 06071 Badajoz, Spain. Electronic address: mbcerezo@unex.es.
authors: María Isabel
authors: MI
authors: Cerezo-Guisado
authors: Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, Campus de Cantoblanco, 28049 Madrid, Spain.
authors: Rafal
authors: R
authors: Zur
authors: Department of Biochemistry and Molecular Biology, Facultad de Veterinaria, Universidad de Extremadura 10071 Cáceres, Spain.
authors: María Jesús
authors: MJ
authors: Lorenzo
authors: Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, Campus de Cantoblanco, 28049 Madrid, Spain.
authors: Ana
authors: A
authors: Risco
authors: Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, Campus de Cantoblanco, 28049 Madrid, Spain.
authors: Miguel A
authors: MA
authors: Martín-Serrano
authors: Servicio de Técnicas Aplicadas a las Biociencias, Universidad de Extremadura, Avda, de Elvas s/n, 06071 Badajoz, Spain.
authors: Alberto
authors: A
authors: Alvarez-Barrientos
authors: Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, Campus de Cantoblanco, 28049 Madrid, Spain. Electronic address: acuenda@cnb.csic.es.
authors: Ana
authors: A
authors: Cuenda
authors: Department of Biochemistry and Molecular Biology, Facultad de Ciencias, Universidad de Extremadura, Avda, de Elvas s/n, 06071 Badajoz, Spain. Electronic address: pacenten@unex.es.
authors: Francisco
authors: F
authors: Centeno
mesh_terms: D016588:Anticarcinogenic Agents / Q000378:metabolism*; D000975:Antioxidants / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D002392:Catechin / Q000031:analogs & derivatives* / Q000378:metabolism; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000201:enzymology / Q000378:metabolism* / Q000517:prevention & control; D005511:Food Handling; D057809:HEK293 Cells; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D009994:Osmolar Concentration; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering; D013662:Tea / Q000737:chemistry; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D016588:Anticarcinogenic Agents; D000975:Antioxidants; D007527:Isoenzymes; D047428:Protein Kinase Inhibitors; D034741:RNA, Small Interfering; D013662:Tea; D002392:Catechin; C045651:epigallocatechin gallate; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Akt; Apoptosis; Colon cancer; EGCG; ERK; p38γ/p38δ