Anti-leukemic response of a NSAID, tolfenamic acid

Robert M. Sutphin, Sarah F. Connelly, Chris M. Lee, Umesh T. Sankpal, Don Eslin, Moeez Khan, Hima Pius, Riyaz Basha

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6 Scopus citations

Abstract

Tolfenamic acid (TA), a non-steroidal anti-inflammatory drug, is known to inhibit human cancer cells and mouse tumor growth in some cancer models; however, its anti-leukemic response has not been evaluated. TA targets specificity protein (Sp) transcription factors that mediate the expression of several genes associated with cancer including survivin, a key member of inhibitor of apoptosis protein family. Our aim was to test the anti-leukemic efficacy of TA in pre-clinical experiments. The anti-leukemic response of TA was determined using Jurkat and Nalm-6 cell lines. Cells were treated with increasing (25/50/75 μM) concentrations of TA, and cell viability was measured at 24, 48, and 72 h post-treatment. TA showed a steady and consistent decrease in cell viability following a clear dose and time dependent response. Apoptosis and cell cycle analysis was performed using flow cytometry. Results showed a significant increase in the apoptotic fraction (annexin V positive) following TA treatment, while cell cycle phase distribution analysis showed G0/G1 arrest. TA-induced apoptosis was further confirmed by examining the activation of caspase 3/7 and the expression of cleaved PARP. TA modulated the expression of critical candidates associated with the early phases of cell cycle and validated its efficacy in causing G0/G 1 arrest. The Western blot results revealed that TA significantly decreases Sp1 and survivin expression. These results demonstrate that the anti-leukemic response of TA occurs potentially through targeting Sp1 and inhibiting survivin and suggest the efficacy of TA as a novel therapeutic agent for leukemia.

Original languageEnglish
Pages (from-to)135-144
Number of pages10
JournalTargeted Oncology
Volume9
Issue number2
DOIs
StatePublished - Jun 2014

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Keywords

  • Leukemia
  • NSAID
  • Sp1
  • Survivin
  • Tolfenamic acid
  • Transcription factors

Cite this

Sutphin, R. M., Connelly, S. F., Lee, C. M., Sankpal, U. T., Eslin, D., Khan, M., Pius, H., & Basha, R. (2014). Anti-leukemic response of a NSAID, tolfenamic acid. Targeted Oncology, 9(2), 135-144. https://doi.org/10.1007/s11523-013-0274-9