Inhibition of myeloid cell leukemia-1 by tolfenamic acid induces apoptosis in mucoepidermoid carcinoma.

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.

• Authors: K-H Choi, J-H Shim, L D Huong, N-P Cho, S-D Cho
• Journal: Oral diseases (Oral Dis) Vol. 17 Issue 5 Pg. 469-75 (Jul 2011) ISSN: 1601-0825 [Electronic] Denmark
• PMID: 21496182 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2010 John Wiley & Sons A/S.

Chemical References

• Antineoplastic Agents
• Coloring Agents
• Cyclooxygenase Inhibitors
• Indoles
• Myeloid Cell Leukemia Sequence 1 Protein
• Nucleic Acid Synthesis Inhibitors
• Proto-Oncogene Proteins c-bcl-2
• RNA, Small Interfering
• Sp1 Transcription Factor
• Tetrazolium Salts
• Thiazines
• Thiazoles
• ortho-Aminobenzoates
• ampiroxicam
• 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium
• tolfenamic acid
• DAPI
• Extracellular Signal-Regulated MAP Kinases
• JNK Mitogen-Activated Protein Kinases
• p38 Mitogen-Activated Protein Kinases
• Caspase 3
• Plicamycin

Topics

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