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.

Anti-interferon gamma action of epigallocatechin-3-gallate mediated by specific inhibition of STAT1 activation.

Menegazzi M.;Tedeschi E.;Dussin D.;De Prati A. C.;Cavalieri E.;Mariotto S.;Suzuki H.
2001

Abstract

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.
green tea; STAT1; NOS-II
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11562/307085
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