Growth factor-dependent induction of p21CIP1 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 p21CIP1/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.