Luteolin is 3',4',5,7-tetrahydroxyflavone found in various kind of fruits and vegetables. We have previously shown that luteolin decreased HT-29 cell growth by inducing apoptosis and cell cycle arrest. The present study examined whether luteolin downregulates ErbB3 signaling pathway in HT-29 cells. Cells were cultured with or without 60Ռmol/L of luteolin and/or heregulin (HRG)-Ղ. HRG-Ղ induced proliferation of HT-29 cells and luteolin abrogated this induction. Luteolin decreased both protein and mRNA levels of EGFR, ErbB3 and ErbB2 in HT-29 cells. Immunoprecipitation/Western blot analyses revealed that luteolin decreased HRG-Ղ-induced tyrosine phosphorylation of ErbB3, recruitment of the p85 subunit of PI3K to ErbB3, and ErbB3-associated PI3K activity. Furthermore luteolin decreased HRG-Ղ-stimulated phosphorylation of Akt. Luteolin also decreased extracellular signal-regulated kinase (ERK)1/2. The present results demonstrate that luteolin down-regulates the ErbB3 signaling pathway, which may one of the mechanisms responsible for the growth inhibitory effect on HT-29 cells. (Cancer Prev Res 16, 134-140, 2011)

Keywords: Luteolin, Colon cancer, ErbB3, Phosphatidylinositol 3-kinase (PI3K), Akt