title: RU486, a glucocorticoid receptor antagonist, induces apoptosis in U937 human lymphoma cells through reduction in mitochondrial membrane potential and activation of p38 MAPK.
abstract: RU486 (mifepristone) exerts an anticancer effect on cancer cells via induction of apoptosis. However, the molecular mechanisms are not fully understood. Here, we investigated the effect of RU486 on the apoptosis of U937 human leukemia cells. RU486 markedly increased apoptosis in U937 cells as well as in MDA231 human breast carcinoma, A549 human lung adenocarcinoma epithelial and HCT116 human colorectal carcinoma cells. RU486 increased dose-dependent release of mitochondrial cytochrome c, and reduced the mitochondrial membrane potential (MMP, Δψm) in RU486-treated U937 cells. We also found that overexpression of Bcl-2 completely blocked RU486-mediated apoptosis. However, reactive oxygen species signaling had no effect on RU486-induced apoptosis. RU486 increased the phosphorylation of p38 MAPK and JNK, but p38 MAPK only was associated with RU486-mediated apoptosis. Taken together, RU486 induces apoptosis through reduction in the mitochondrial membrane potential and activation of p38 MAPK in U937 human leukemia cells.
authors.affiliation: Department of Immunology, School of Medicine, Keimyung University, Dalseo-Gu, Daegu, Republic of Korea.
authors.forename: Ji Hoon
authors.initials: JH
authors.lastname: Jang
authors.forename: Seon Min
authors.initials: SM
authors.lastname: Woo
authors.forename: Hee Jung
authors.initials: HJ
authors.lastname: Um
authors.forename: Eun Jung
authors.initials: EJ
authors.lastname: Park
authors.forename: Kyoung-Jin
authors.initials: KJ
authors.lastname: Min
authors.forename: Tae-Jin
authors.initials: TJ
authors.lastname: Lee
authors.forename: Sang Hyun
authors.initials: SH
authors.lastname: Kim
authors.forename: Yung Hyun
authors.initials: YH
authors.lastname: Choi
authors.forename: Taeg Kyu
authors.initials: TK
authors.lastname: Kwon
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy; D000077192:Adenocarcinoma of Lung; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000188:drug therapy; D045304:Cytochromes c / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D045325:HCT116 Cells; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy; D008223:Lymphoma / Q000188:drug therapy* / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D015735:Mifepristone / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors; D020298:U937 Cells; D048051:p38 Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism
chemical_list: D006727:Hormone Antagonists; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D011965:Receptors, Glucocorticoid; D015735:Mifepristone; D045304:Cytochromes c; D048051:p38 Mitogen-Activated Protein Kinases