title: Isoliquiritigenin induces apoptosis by depolarizing mitochondrial membranes in prostate cancer cells.
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 micromol/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 caspase-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.
authors.affiliation: Department of Food Science and Nutrition, Hallym University, Chuncheon 200-702, South Korea.
authors.forename: Jae In
authors.initials: JI
authors.lastname: Jung
authors.forename: Soon Sung
authors.initials: SS
authors.lastname: Lim
authors.forename: Hyun Ju
authors.initials: HJ
authors.lastname: Choi
authors.forename: Han Jin
authors.initials: HJ
authors.lastname: Cho
authors.forename: Hyun-Kyung
authors.initials: HK
authors.lastname: Shin
authors.forename: Eun Ji
authors.initials: EJ
authors.lastname: Kim
authors.forename: Won-Yoon
authors.initials: WY
authors.lastname: Chung
authors.forename: Kwang-Kyun
authors.initials: KK
authors.lastname: Park
authors.forename: Jung Han Yoon
authors.initials: JH
authors.lastname: Park
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D020169:Caspases / Q000032:analysis / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002599:Chalcone / Q000031:analogs & derivatives* / Q000494:pharmacology; D047188:Chalcones; D045304:Cytochromes c / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D053222:Fas Ligand Protein; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D008564:Membrane Potentials / Q000187:drug effects; D051336:Mitochondrial Membranes / Q000187:drug effects* / Q000502:physiology; D011065:Poly(ADP-ribose) Polymerases / Q000032:analysis; D011471:Prostatic Neoplasms / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D051381:Rats; D048069:Tumor Necrosis Factors / Q000032:analysis; D019014:fas Receptor / Q000032:analysis
chemical_list: D047188:Chalcones; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505662:Faslg protein, rat; D008562:Membrane Glycoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D048069:Tumor Necrosis Factors; D019014:fas Receptor; D002599:Chalcone; D045304:Cytochromes c; C040920:isoliquiritigenin; D011065:Poly(ADP-ribose) Polymerases; D020169:Caspases