Growth factor-dependent induction of p21(CIP1) by the green tea by polyphenol, epigallocatechin gallate

Tea polyphenols inhibit tumorigenesis and cell proliferation in rodent mode ls, but their effects on cell signaling and cell cycle control pathways are undefined. Here, we show that the major polyphenol in green tea, epigalloc atechin gallate (EGCG), inhibits S phase entry in epidermal growth factor ( EGF)- stimulated MCF10A breast epithelial cells when provided in GO or mid G1, bur not when provided after the late G1 restriction point. EGCG induced p21(CIP1/WAF1/SDII), inhibited cyclin D1-associated pRB kinase activity, a nd impaired pRB phosphorylation. The ability of EGCG to induce p21 depended upon the addition of EGF, indicating that EGCG synergizes with growth fact or-dependent signals to induce p21 and impair cell cycle progression.. (C) 2000 published by Elsevier Science Ireland Ltd. All rights reserved.