Abstract
Objectives:
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).
Materials and 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.
Conclusion:
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.
© 2010 John Wiley & Sons A/S.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents / pharmacology*
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Apoptosis / drug effects*
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Blotting, Western
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Carcinoma, Mucoepidermoid / pathology*
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Caspase 3 / drug effects
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Cell Nucleus / drug effects
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Cell Proliferation / drug effects
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Coloring Agents
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Cyclooxygenase Inhibitors / pharmacology
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Enzyme Activation
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Extracellular Signal-Regulated MAP Kinases / pharmacology
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G1 Phase / drug effects
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Humans
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Immunohistochemistry
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Indoles
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JNK Mitogen-Activated Protein Kinases / pharmacology
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Myeloid Cell Leukemia Sequence 1 Protein
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Nucleic Acid Synthesis Inhibitors / pharmacology
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Plicamycin / pharmacology
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Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors*
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RNA, Small Interfering / genetics
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Reverse Transcriptase Polymerase Chain Reaction
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Salivary Gland Neoplasms / pathology*
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Sp1 Transcription Factor / pharmacology
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Tetrazolium Salts
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Thiazines / pharmacology
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Thiazoles
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Transfection
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Tumor Cells, Cultured
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ortho-Aminobenzoates / pharmacology*
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p38 Mitogen-Activated Protein Kinases / pharmacology
Substances
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Antineoplastic Agents
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Coloring Agents
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Cyclooxygenase Inhibitors
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Indoles
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Myeloid Cell Leukemia Sequence 1 Protein
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Nucleic Acid Synthesis Inhibitors
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Proto-Oncogene Proteins c-bcl-2
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RNA, Small Interfering
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Sp1 Transcription Factor
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Tetrazolium Salts
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Thiazines
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Thiazoles
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ortho-Aminobenzoates
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ampiroxicam
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3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium
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tolfenamic acid
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DAPI
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Extracellular Signal-Regulated MAP Kinases
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JNK Mitogen-Activated Protein Kinases
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p38 Mitogen-Activated Protein Kinases
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Caspase 3
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Plicamycin