Isoliquiritigenin induces apoptosis by depolarizing mitochondrial membranes in prostate cancer cells.
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.
Jung
Jae In
JI
Department of Food Science and Nutrition, Hallym University, Chuncheon 200-702, South Korea.
Lim
Soon Sung
SS
Choi
Hyun Ju
HJ
Cho
Han Jin
HJ
Shin
Hyun-Kyung
HK
Kim
Eun Ji
EJ
Chung
Won-Yoon
WY
Park
Kwang-Kyun
KK
Park
Jung Han Yoon
JH
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
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