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Effect of isoliquiritigenin (ISL) on insulin‐like growth factor‐I receptor and ErbB3 signaling in prostate cancer cells
Author(s) -
Jung Jae In,
Seon Mi Ra,
Shin HyunKyung,
Lim Soon Sung,
Chung WonYoon,
Park Jung Han Yoon
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a569-c
Subject(s) - isoliquiritigenin , insulin like growth factor , prostate cancer , erbb3 , cancer research , cancer , medicine , receptor , endocrinology , oncology , growth factor , epidermal growth factor receptor , pharmacology
The insulin‐like growth factor (IGF) system has been implicated as a risk factor for the development of several human cancers. In addition, over‐expression of members of the ErbB receptor family is frequent event in several human cancers. The chalcone ISL has been recognized as a potent anti‐tumor promoting agent. We previously demonstrated that ISL decreased cell proliferation and induced apoptosis in prostate cancer cells. To examine the mechanisms underlying ISL regulation of prostate cancer cell growth, DU145 human prostate cancer cells and MAT‐LyLu (MLL) rat prostate cancer cells were cultured in serum‐free medium with various concentrations of ISL and/or IGF‐I or heregulin‐β (HRG). Exogenous IGF‐I or HRG alone increased viable cell numbers, whereas neither IGF‐I nor HRG counteracted growth inhibition induced by ISL. ISL decreased the protein and mRNA levels of IGF‐I receptor (IGF‐IR) and ErbB in does‐dependent manners. Immunoprecipitation/Western blot studies showed that ISL inhibited IGF‐I‐induced phosphorylation of IGF‐IR, recruitment of the p85 subunit of phosphoinositide 3‐kinase (PI3K) to IGF‐IR and phosphorylation of Akt in MLL and DU145 cells. In addition, ISL inhibited HRG‐induced phosphorylation of ErbB3, recruitment of p85 to ErbB3 and phosphorylation of Akt in DU145 cells. These results indicate that ISL inhibits proliferation of prostate cancer cells via its inhibition of IGF‐IR and ErbB3 signaling and the PI3K/Akt pathway.