Anti-leukemic response of a NSAID, tolfenamic acid

    Authors

    R. M. Sutphin; S. F. Connelly; C. M. Lee; U. T. Sankpal; D. Eslin; M. Khan; H. Pius;R. Basha

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    Abbreviated Journal Title

    Target. Oncol.

    Keywords

    Leukemia; Tolfenamic acid; Sp1; Survivin; Transcription factors; NSAID; ACUTE LYMPHOBLASTIC-LEUKEMIA; ENDOTHELIAL GROWTH-FACTOR; HUMAN; NEUROBLASTOMA-CELLS; IAP FAMILY PROTEINS; BREAST-CANCER CELLS; TARGETING; SURVIVIN; CHILDHOOD LEUKEMIA; TUMOR-GROWTH; IN-VIVO; SP1; Oncology

    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 mu M) 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 G(0)/G(1) 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 G(0)/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.

    Journal Title

    Targeted Oncology

    Volume

    9

    Issue/Number

    2

    Publication Date

    1-1-2014

    Document Type

    Article

    Language

    English

    First Page

    135

    Last Page

    144

    WOS Identifier

    WOS:000337055400004

    ISSN

    1776-2596

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