title: Inhibition of myeloid cell leukemia-1 by tolfenamic acid induces apoptosis in mucoepidermoid carcinoma.
abstract: OBJECTIVE
  The aim of this study was to evaluate the role of tolfenamic acid (Tol) and ampiroxicam (Amp) in the apoptotic regulation of YD-15 salivary mucoepidermoid carcinoma (MEC).
  
  
  METHODS
  The effect of Tol on apoptosis and its mechanism were examined using a 3-(4,5-dimethylthiazol-2-yl)-5-(2,4-disulfophenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay, Sub-G(1) population, Western blot analysis, 4'-6-Diamidino-2-phenylindole staining, reverse transcriptase polymerase chain reaction, immunostaining and small interfering RNA transfection.
  
  
  RESULTS
  Tol inhibited cell growth of YD-15 cells but Amp did not. Tol induces apoptosis in YD-15 cells as evidenced by nuclear fragmentation, accumulation of the sub-G1 phase and the activation of caspase 3. Tol inhibited myeloid cell leukemia-1 (MCL-1) at the protein and mRNA levels. The treatment of MCL-1 siRNA to YD-15 cells resulted in the activation of caspase 3 and the inhibition of cell growth. Moreover, MCL-1 was regulated by specificity protein 1, but not by mitogen-activated protein kinases.
  
  
  CONCLUSIONS
  These results suggest that Tol could be a potent anti-cancer drug for YD-15 MEC cells that acts by regulating the MCL-1 protein.
authors.affiliation: Department of Oral Pathology, School of Dentistry and Institute of Oral Bioscience, Brain Korea 21 Project, Chonbuk National University, Jeon-ju, Korea.
authors.forename: K-H
authors.initials: KH
authors.lastname: Choi
authors.forename: J-H
authors.initials: JH
authors.lastname: Shim
authors.forename: L D
authors.initials: LD
authors.lastname: Huong
authors.forename: N-P
authors.initials: NP
authors.lastname: Cho
authors.forename: S-D
authors.initials: SD
authors.lastname: Cho
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D018277:Carcinoma, Mucoepidermoid / Q000473:pathology*; D053148:Caspase 3 / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004396:Coloring Agents; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000494:pharmacology; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D007211:Indoles; D048031:JNK Mitogen-Activated Protein Kinases / Q000494:pharmacology; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D008926:Plicamycin / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors*; D034741:RNA, Small Interfering / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012468:Salivary Gland Neoplasms / Q000473:pathology*; D016329:Sp1 Transcription Factor / Q000494:pharmacology; D013778:Tetrazolium Salts; D013843:Thiazines / Q000494:pharmacology; D013844:Thiazoles; D014162:Transfection; D014407:Tumor Cells, Cultured; D062367:ortho-Aminobenzoates / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D004396:Coloring Agents; D016861:Cyclooxygenase Inhibitors; D007211:Indoles; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019384:Nucleic Acid Synthesis Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D016329:Sp1 Transcription Factor; D013778:Tetrazolium Salts; D013843:Thiazines; D013844:Thiazoles; D062367:ortho-Aminobenzoates; C065946:ampiroxicam; C070380:3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium; C009500:tolfenamic acid; C007293:DAPI; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D053148:Caspase 3; D008926:Plicamycin