title: Isoliquiritigenin, a natural anti-oxidant, selectively inhibits the proliferation of prostate cancer cells.
abstract: 1. Isoliquiritigenin (ISL) is a simple chalcone-type flavonoid derived from liquorice compounds. It has been reported to have anti-oxidative and antitumour activities. The aim of the present study was to investigate the antitumour effect of ISL on prostate cancer cells and to explore the possible signalling mechanisms involved. 2. Cell viability was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The fluorescent probe 2',7'-dichlorofluorescein diacetate (H(2)DCF-DA) was used to measure intracellular levels of reactive oxygen species (ROS). Mitochondrial membrane potential (Psi(m)) was measured using the mitochondrial probe 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethyl-benzimidazolylcarbocyanine iodide (JC-1). 3. Isoliquiritigenin treatment (10-100 micromol/L for 24 h) markedly inhibited the proliferation of both C4-2 and LNCaP prostate cancer cells in a dose-dependent manner. Intriguingly, ISL treatment (10-100 micromol/L for 24 h) had no effect on the viability of IEC-6 normal epithelial cells. Treatment of C4-2 and IEC-6 cells with 87.0 micromol/L ISL significantly decreased ROS levels and the Psi(m) of C4-2 cells, but had no effect on either parameter in IEC-6 cells. Furthermore, AMP-activated protein kinase (AMPK) and extracellular-signal regulated kinase (ERK) levels were three to fourfold higher in IEC-6 cells than in C4-2 cells (P < 0.05). 4. The results of the present study suggest that ISL, a natural anti-oxidant, selectively inhibits the proliferation of prostate cancer C4-2 cells, which may be attributed, in part, to defective AMPK and ERK signalling pathways in C4-2 compared with IEC-6 cells.
authors.affiliation: School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu, China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Zhang
authors.forename: Eddie D
authors.initials: ED
authors.lastname: Yeung
authors.forename: Jingying
authors.initials: J
authors.lastname: Wang
authors.forename: Evgeniy E
authors.initials: EE
authors.lastname: Panzhinskiy
authors.forename: Chao
authors.initials: C
authors.lastname: Tong
authors.forename: Wenguang
authors.initials: W
authors.lastname: Li
authors.forename: Ji
authors.initials: J
authors.lastname: Li
mesh_terms: D000972:Antineoplastic Agents, Phytogenic; D000975:Antioxidants / Q000494:pharmacology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D047188:Chalcones / Q000494:pharmacology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051336:Mitochondrial Membranes / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D013778:Tetrazolium Salts; D013844:Thiazoles; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D000975:Antioxidants; D047188:Chalcones; D016166:Free Radical Scavengers; D013778:Tetrazolium Salts; D013844:Thiazoles; C040920:isoliquiritigenin; D017868:Cyclic AMP-Dependent Protein Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C022616:thiazolyl blue