title: Glycyrrhizic acid induces apoptosis in WEHI-3 mouse leukemia cells through             the caspase- and mitochondria-dependent pathways.
abstract: Leukemia, one of the causes of cancer-related death in humans, is an aggressive             malignancy via the rapid growth of abnormal white blood cells. The aim of this             study was to determine the anti-leukemia effect of glycyrrhizic acid (GA) on a             mouse leukemia cell line, WEHI-3. GA, an active compound in Glycyrrhiza glabra,             has been proven to induce cytotoxic effects in many cancer cell lines. In the             current study, we investigated the effects of GA in mouse leukemia cells in vitro.             The results indicated that GA induced morphological changes, G0/G1 phase arrest,             apoptosis and DNA damage in WEHI-3 cells as determined by phase contrast microscopy,             DAPI-staining, flow cytometry and comet assay. The results from the flow cytometric             assay showed that GA increased ROS levels, reduced the mitochondrial membrane             potential (ΔΨm) and stimulated caspase-3 activity in WEHI-3 cells. GA regulated             the intrinsic and extrinsic apoptosis-associated protein expression which was             determined by western blotting. In addition, endoplasmic reticulum (ER) stress             responses were observed in GA-treated WEHI-3 cells. GA promoted the trafficking             of apoptosis-inducing factor (AIF), cytochrome c and endonuclease G (Endo G) in             WEHI-3 cells. Based on this evidence, GA-triggered apoptosis occurs through the             death receptor, mitochondria-mediated and ER stress multiple signaling pathways.
authors.affiliation: Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan, ROC.
authors.forename: Fu-Shin
authors.initials: FS
authors.lastname: Chueh
authors.forename: Yung-Ting
authors.initials: YT
authors.lastname: Hsiao
authors.forename: Shu-Jen
authors.initials: SJ
authors.lastname: Chang
authors.forename: Ping-Ping
authors.initials: PP
authors.lastname: Wu
authors.forename: Jai-Sing
authors.initials: JS
authors.lastname: Yang
authors.forename: Jen-Jyh
authors.initials: JJ
authors.lastname: Lin
authors.forename: Jing-Gung
authors.initials: JG
authors.lastname: Chung
authors.forename: Tung-Yuan
authors.initials: TY
authors.lastname: Lai
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects; D004706:Endodeoxyribonucleases / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D019695:Glycyrrhizic Acid / Q000494:pharmacology*; D007938:Leukemia / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D017382:Reactive Oxygen Species; D053218:Receptors, Death Domain / Q000378:metabolism
chemical_list: D051033:Apoptosis Inducing Factor; D017382:Reactive Oxygen Species; D053218:Receptors, Death Domain; D019695:Glycyrrhizic Acid; D045304:Cytochromes c; D004706:Endodeoxyribonucleases; C052391:endonuclease G; D053148:Caspase 3