Isoliquiritigenin (ISL), a
flavonoid found in licorice, shallot, and bean sprouts, has been identified as a potent anti-
tumor promoting agent. We previously demonstrated that ISL reduces cell proliferation and induces apoptosis in DU145 human
prostate cancer cells and MAT-LyLu (MLL) rat
prostate cancer cells. Overexpression of members of the
ErbB receptor family is a frequently observed event in several human
cancers, and
ErbB receptors currently constitute the primary targets of anticancer strategies. In order to elucidate the mechanisms underlying the ISL regulation of
prostate cancer cell proliferation, the present study attempted to determine whether ISL inhibits
heregulin (
HRG)-beta-induced ErbB3 signaling. DU145 and MLL cells were cultured in serum-free medium with ISL and/or
HRG-beta. Exogenous
HRG-beta alone was shown to effect an increase in the numbers of viable cells, whereas
HRG-beta did not counteract the ISL-induced growth inhibition. ISL reduced the
protein and
mRNA levels of ErbB3 in a dose-dependent manner, but exerted no effect on
HRG protein levels. Immunoprecipitation/Western blot studies indicated that ISL inhibited the
HRG-beta-induced
tyrosine phosphorylation of ErbB3, the recruitment of the p85 regulatory subunit of
phosphatidylinositol 3-kinase (PI3K) to ErbB3, and Akt phosphorylation in DU145 cells. These results indicate that ISL inhibits the proliferation of
prostate cancer cells, at least in part, via the inhibition of ErbB3 signaling and the PI3K/Akt pathway.