Affiliations: Department of Food Science and Nutrition and Silver
Biotechnology Research Center, Hallym University, Chuncheon, Korea | Department of Biomedical Science, Hallym University,
Chuncheon, Korea | Department of Oral Biology, College of Dentistry,
Yonsei University, Seoul, 120-752, Korea
Note: [] Address for correspondence: Jung H.Y. Park, Department of Food
Science and Nutrition, Hallym University, 39 Hallymdaehak-gil, Chuncheon,
200-702, Korea. Tel.: +82 33 248 2134; Fax: +82 33 256 0199; E-mail:
[email protected]
Abstract: 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)-β-induced ErbB3 signaling. DU145 and MLL
cells were cultured in serum-free medium with ISL and/or
HRG-β. Exogenous HRG-β alone was
shown to effect an increase in the numbers of viable cells, whereas
HRG-β 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-β-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.
