tolfenamic-acid and ampiroxicam

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).. 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.. 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.. 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.

Topics: Antineoplastic Agents; Apoptosis; Blotting, Western; Carcinoma, Mucoepidermoid; Caspase 3; Cell Nucleus; Cell Proliferation; Coloring Agents; Cyclooxygenase Inhibitors; Enzyme Activation; Extracellular Signal-Regulated MAP Kinases; G1 Phase; Humans; Immunohistochemistry; Indoles; JNK Mitogen-Activated Protein Kinases; Myeloid Cell Leukemia Sequence 1 Protein; Nucleic Acid Synthesis Inhibitors; ortho-Aminobenzoates; p38 Mitogen-Activated Protein Kinases; Plicamycin; Proto-Oncogene Proteins c-bcl-2; Reverse Transcriptase Polymerase Chain Reaction; RNA, Small Interfering; Salivary Gland Neoplasms; Sp1 Transcription Factor; Tetrazolium Salts; Thiazines; Thiazoles; Transfection; Tumor Cells, Cultured