The Polyphenols (−)-Epigallocatechin-3-Gallate and Luteolin Synergistically Inhibit TGF-β-Induced Myofibroblast Phenotypes through RhoA and ERK Inhibition

摘要: The presence of reactive stroma, predominantly composed myofibroblasts, is directly associated with and drives prostate cancer progression. We have previously shown that (−)-Epigallocatechin-3-gallate (EGCG), in the form Polyphenon E, significantly decreases serum levels HGF VEGF patients. Given are secreted from surrounding tumor these observations suggested EGCG may inhibit cancer-associated myofibroblast differentiation. Herein, we demonstrate micromolar combinations a second polyphenol, luteolin, synergistically TGF-β-induced phenotypes fibroblast cell lines, as observed primarily by potentiation fibronectin expression. Functionally, luteolin inhibited extracellular matrix contraction, an enhancer invasion. downstream signaling, including activation ERK AKT, respectively, but mechanistically, only appeared to be necessary for Furthermore, neither nor affected Smad signaling or nuclear translocation. Rho was found expression each reduced RhoA activation. Finally, were reverse expression, implicating natural compounds useful not preventing also treating already activated myofibroblasts diseases they cause, cancer. ability target suggests combined clinical use could prevent progression through targeting microenvironment, addition itself.