title: Liquiritigenin induces tumor cell death through mitogen-activated protein kinase- (MPAKs-) mediated pathway in hepatocellular carcinoma cells.
abstract: Liquiritigenin (LQ), separated from Glycyrrhiza radix, possesses anti-inflammatory, antihyperlipidemic, and antiallergic effects. Our present study aims to investigate the antihepatocellular carcinoma effects of LQ both in cell and animal models. LQ strikingly reduced cell viability, enhanced apoptotic rate, induced lactate dehydrogenase over-release, and increased intracellular reactive oxygen species (ROS) level and caspase 3 activity in both PLC/PRL/5 and HepG2 cells. The expression of cleaved PARP, the hall-marker of apoptosis, was enhanced by LQ. LQ treatment resulted in a reduction of the expressions of B-cell lymphoma 2 (Bcl-2) and B-cell lymphoma-extra large (Bcl-xL), and an increase of the phosphorylation of c-Jun N-terminal kinases (JNK) and P38. LQ-mediated cell viability reduction, mitochondrial dysfunction, apoptosis related protein abnormal expressions, and JNK and P38 activation were partially abolished by N-Acetyl-L-cysteine (a ROS inhibitor) pretreatment. Moreover, LQ suppressed the activation of extracellular signaling-regulated kinase (ERKs) and reduced the translocation of phosphor-ERKs from cytoplasm to nucleus. This antitumor activity was further confirmed in PLC/PRL/5-xenografted mice model. All these data indicate that the antihepatocellular carcinoma effects of LQ are related to its modulation of the activations of mitogen-activated protein kinase (MAPKs). The study provides experimental evidence supporting LQ as a potential therapeutic agent for hepatocellular carcinoma treatment.
authors.affiliation: College of Life Science, Jilin University, Changchun, Jilin 130012, China ; The State Engineering Laboratory of AIDS Vaccine, Jilin University, Changchun 130012, China.
authors.forename: Di
authors.identifier: 0000-0002-7322-4174
authors.initials: D
authors.lastname: Wang
authors.affiliation: College of Life Science, Jilin University, Changchun, Jilin 130012, China.
authors.forename: Jiahui
authors.initials: J
authors.lastname: Lu
authors.affiliation: College of Life Science, Jilin University, Changchun, Jilin 130012, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: College of Life Science, Jilin University, Changchun, Jilin 130012, China.
authors.forename: Qingfan
authors.initials: Q
authors.lastname: Meng
authors.affiliation: College of Life Science, Jilin University, Changchun, Jilin 130012, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xie
authors.affiliation: College of Life Science, Jilin University, Changchun, Jilin 130012, China.
authors.forename: Zhenzuo
authors.initials: Z
authors.lastname: Wang
authors.affiliation: College of Life Science, Jilin University, Changchun, Jilin 130012, China ; The State Engineering Laboratory of AIDS Vaccine, Jilin University, Changchun 130012, China.
authors.forename: Lesheng
authors.identifier: 0000-0003-1623-5384
authors.initials: L
authors.lastname: Teng
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D044950:Flavanones / Q000008:administration & dosage*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000096:biosynthesis; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology; D020928:Mitogen-Activated Protein Kinases / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D044950:Flavanones; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; C083152:liquiritigenin
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