Growth factor-dependent induction of p21(CIP1) by the green tea polyphenol, epigallocatechin gallate.
Tea polyphenols inhibit tumorigenesis and cell proliferation in rodent models, but their effects on cell signaling and cell cycle control pathways are undefined. Here, we show that the major polyphenol in green tea, epigallocatechin gallate (EGCG), inhibits S phase entry in epidermal growth factor (EGF) - stimulated MCF10A breast epithelial cells when provided in G0 or mid G1, but not when provided after the late G1 restriction point. EGCG induced p21(CIP1/WAF1/SDI1), inhibited cyclin D1-associated pRB kinase activity, and impaired pRB phosphorylation. The ability of EGCG to induce p21 depended upon the addition of EGF, indicating that EGCG synergizes with growth factor-dependent signals to induce p21 and impair cell cycle progression.
Liberto
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Department of Medicine, Division of Medical Oncology, Columbia University College College of Physicians and Surgeons, Columbia University, 650 West 168th Street BB2009, NY, NY 10032, USA.
Cobrinik
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D000970:Antineoplastic Agents / Q000494:pharmacology; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013662:Tea; D013997:Time Factors
D000970:Antineoplastic Agents; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004791:Enzyme Inhibitors; D006133:Growth Substances; D016160:Retinoblastoma Protein; D013662:Tea; D004815:Epidermal Growth Factor; D002392:Catechin; C045651:epigallocatechin gallate; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases