title: A3 adenosine receptor antagonist, truncated Thio-Cl-IB-MECA, induces apoptosis in T24 human bladder cancer cells.
abstract: BACKGROUND
  Human A(3) adenosine receptor (A(3)AR) plays an essential role in several physiopathological processes. Thus far, A(3)AR-selective ligands have been evaluated as anti-inflammation and anticancer therapeutic agents. Among these ligands, truncated thio-Cl-IB-MECA is a newly reported antagonist, and its function has not been studied.
  
  
  METHODS
  Cell viability was measured by MTS assay. Cell cycle progression was analysed by propidium iodide (PI) flow cytometric assay. The apoptotic effects were investigated by Hoechst staining and annexin V-FITC/PI staining. The signal-transduction mechanism was explored by Western blot.
  
  
  RESULTS
  Truncated thio-Cl-IB-MECA induced the growth arrest of T24 cells at sub-G(1) phase and provoked apoptosis but not necrosis. Apoptotic death was mediated by the activation of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK).
  
  
  CONCLUSIONS
  Since truncated thio-Cl-IB-MECA induces anti-proliferation and apoptotic effects via ERK and JNK activation, it may function as an anticancer agent in human bladder cancer cells.
authors.affiliation: Departments of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University Hwayang-dong 1, Gwangjin-gu, Seoul 143-701, S. Korea.
authors.forename: Heejong
authors.initials: H
authors.lastname: Kim
authors.forename: Jeong Woo
authors.initials: JW
authors.lastname: Kang
authors.forename: Sojung
authors.initials: S
authors.lastname: Lee
authors.forename: Won Jun
authors.initials: WJ
authors.lastname: Choi
authors.forename: Lak Shin
authors.initials: LS
authors.lastname: Jeong
authors.forename: Young
authors.initials: Y
authors.lastname: Yang
authors.forename: Jin Tae
authors.initials: JT
authors.lastname: Hong
authors.forename: Do Young
authors.initials: DY
authors.lastname: Yoon
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D058918:Adenosine A3 Receptor Antagonists; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D058918:Adenosine A3 Receptor Antagonists; C494826:BAX protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C504222:thio-Cl-IB-MECA; D045304:Cytochromes c; D048049:Extracellular Signal-Regulated MAP Kinases; D048670:MAP Kinase Kinase 4; D020169:Caspases; D000241:Adenosine