Anti-leukemic response of a NSAID, tolfenamic acid
Abbreviated Journal Title
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
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.
"Anti-leukemic response of a NSAID, tolfenamic acid" (2014). Faculty Bibliography 2010s. 6154.