Isoliquiritigenin (ISL) inhibits ErbB3 signaling in prostate cancer cells.
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.
Jung
Jae In
JI
Department of Food Science and Nutrition and Silver Biotechnology Research Center, Hallym University, Chuncheon, Korea.
Chung
Eunkyung
E
Seon
Mi Ra
MR
Shin
Hyun-Kyung
HK
Kim
Eun Ji
EJ
Lim
Soon Sung
SS
Chung
Won-Yoon
WY
Park
Kwang-Kyun
KK
Park
Jung Han Yoon
JH
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D047188:Chalcones / Q000494:pharmacology*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D008297:Male; D020890:Neuregulin-1 / Q000037:antagonists & inhibitors; D011471:Prostatic Neoplasms / Q000503:physiopathology; D051381:Rats; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors; D020893:Receptor, ErbB-3 / Q000037:antagonists & inhibitors*; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured
D016588:Anticarcinogenic Agents; D047188:Chalcones; D066246:ErbB Receptors; D020890:Neuregulin-1; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; C040920:isoliquiritigenin