A great interest is emerging about green tea as a tool against human cancer development or inflammation, as pointed out by recent reports describing the inhibitory action of epigallocatechin gallate (EGCG), the main polyphenol component of green tea, on angiogenesis, urokinase, metalloproteinases, and induction of inducible nitric oxide synthase (NOS II). We proposed that EGCG may modulate a cell factor having wider spectra of action than those actions of single enzymes. Signal transducers and activators of transcription (STATs) are nuclear factors mediating the action of cytokines involved in various biological functions. Based on the knowledge that interferon (IFN)-γ-elicited STAT1 activation is important for NOS II expression and that STAT1 critically modulates proliferative and inflammatory processes, we hypothesized that STAT1 could be a target of EGCG. Here we show that 1) in human MDA-MB 231 cell line EGCG blocks IFN-γ-elicited activation of STAT1 by interfering with tyrosine phosphorylation; 2) EGCG suppresses the IFN-γ-elicited expression of NOS II as well as interferon regulating factor-1 (IRF-1); 3) EGCG inhibits IFN-γ-elicited STAT1 activation also in human HeLa, MCF7, MDA MB 468, and HepG2 cells; and 4) EGCG has no effect on interleukin (IL)-6-elicited STAT3 activation in IL6-responsive cells. These results indicate that EGCG could be used as a harmless drug to modulate STAT1 signaling in inflammatory processes and, in some cases, tumor formation.Key words: tumor • inflammation • green tea • tyrosine phosphorylation • inducible nitric oxide synthase • IRF-1 pidemiologic studies and experimental investigations have demonstrated that green tea has an inhibitory effect towards tumor formation and growth (1-4) and inflammation (5-7). Although the antioxidative property of catechins present in green tea such as EGCG and EGC is tentatively accounted for the reported inhibitory activity of green tea (1), the molecular basis of the action of catechins has for long time been elusive. Only recently some hints on the possible molecular mechanism of the antitumor or antiinflammatory effect of green tea have emerged. Epigallocatechin gallate (EGCG), the main polyphenol present in green tea E (8), inhibits urokinase (9), an enzyme indispensable for tumor invasion and metastasis, and angiogenesis (10), which is crucial for the growth of almost all types of tumor. In addition, EGCG efficiently suppresses the activity of matrix metalloproteinase-2 and -9, essential for tumor cells in cutting through basement membrane barriers (11), thus leading to an efficient inhibition of angiogenesis. EGCG also blocks the induction of the expression of NOS II in lipopolysaccharide (LPS)-activated mouse macrophages (12). NOS II, normally silent, is induced, not only in immune cells but also in many other human cell types by cytokines such as interferon γ (IFN-γ), tumor necrosis factor α (TNF-α), and interleukine1 β (IL1-β) in proinflammatory processes (13). Massive amounts of NO produced by NOS II may, on one side, be beneficial fo...