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

Oral Dis. 2011 Jul;17(5):469-75. doi: 10.1111/j.1601-0825.2010.01774.x. Epub 2010 Dec 23.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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

Substances

  • 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