The Journal of Nutritional Biochemistry
Volume 17, Issue 10 , October 2006, Pages 689-696
doi:10.1016/j.jnutbio.2005.11.006 
Copyright © 2006 Elsevier Inc. All rights reserved.
Research article
Isoliquiritigenin
induces apoptosis by depolarizing mitochondrial membranes in prostate cancer cells
Jae In Junga, Soon Sung Lima, b, Hyun Ju Choia, Han Jin Chob, Hyun-Kyung Shina, b, Eun Ji Kimb, Won-Yoon Chungc, Kwang-Kyun Parkc and Jung Han Yoon Parka, b, 
, 
aDepartment of Food Science and Nutrition, Hallym University, Chuncheon 200-702, South Korea
bSilver Biotechnology Research Center, Hallym University, Chuncheon 200-702, South Korea
cDepartment of Oral Biology, College of Dentistry, Yonsei University, Seoul 120-752, South Korea
Received 13 October 2005; revised 8 November 2005; accepted 9 November 2005. Available online 9 December 2005.
Abstract
Isoliquiritigenin (ISL), a simple chalcone derivative, 4,2′,4′-trihydroxychalcone, found in licorice, shallot and bean sprouts, has been reported to have chemoprotective effects. To examine the effects of ISL on the growth of prostate cancer cells, we cultured MAT-LyLu (MLL) rat and DU145 human prostate cancer cells with various concentrations (0–20 μmol/L) of ISL. Treatment of the cells with increasing concentrations of ISL led to dose-dependent decreases in the viable cell numbers in both DU145 and MLL cells (P<.05). Hoechst 33258 dye staining of condensed nuclei and annexin V binding to surface phosphatidylserine revealed increased numbers of apoptotic cells after ISL treatment. Western blot analysis revealed that ISL increased the levels of membrane-bound Fas ligand (FasL), Fas, cleaved casapse-8, truncated Bid (tBid), Bax and Bad in DU145 cells (P<.05). Isoliquiritigenin increased the percentage of cells with depolarized mitochondrial membranes, in a concentration-dependent manner (P<.05). Isoliquiritigenin induced the release of cytochrome c and Smac/Diablo from the mitochondria into the cytoplasm (P<.05). Isoliquiritigenin dose-dependently increased the levels of cleaved caspsase-9, caspase-7, caspase-3 and poly(ADP-ribose) polymerase (P<.05). The present results indicate that ISL inhibits prostate cancer cell growth by the induction of apoptosis, which is mediated through mitochondrial events, which are associated with an evident disruption of the mitochondrial membrane potential, and the release of cytochrome c and Smac/Diablo, and the activation of caspase-9.
Keywords: Bcl-2; Caspase; Apoptosis; Cytochrome c; Prostate cancer cells
Abbreviations: ISL, isoliquiritigenin; MLL, MAT-LyLu; PARP, poly(ADP-ribose) polymerase
