Isoliquiritigenin (ISL) inhibits ErbB3 signaling in prostate cancer cells
Jae In Jung A1, Eunkyung Chung A2, Mi Ra Seon A1, Hyun-Kyung Shin A1, Eun Ji Kim A1, Soon Sung Lim A1, Won-Yoon Chung A3, Kwang-Kyun Park A3, Jung Han Yoon Park A3
A1 Department of Food Science and Nutrition and Silver Biotechnology Research Center, Hallym University, Chuncheon, Korea A2 Department of Biomedical Science, Hallym University, Chuncheon, Korea A3 Department of Oral Biology, College of Dentistry, Yonsei University, Seoul, 120-752, Korea
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.
Keywords:
Isoliquiritigenin, prostate cancer cells, ErbB signaling, Akt, phosphatidylinositol 3-kinase, ERK-1/2
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