Tolfenamic Acid and its metal complex: anti-cancer effects on medulloblastoma cells

Purpose: Medulloblastoma is the most common pediatric brain cancer. Current treatment options often leave survivors with lifelong cognitive deficits, prompting the need to identify non-toxic therapies. Tolfenamic Acid(TA), a non-steroidal anti-inflammatory drug(NSAID), demonstrated anti-proliferation activity in medulloblastoma cells and is known to down-regulate expression of anti-apoptotic protein Survivin. This study seeks to compare the effects of TA to a newly developed copper complex, (CuTA). We hypothesize that the CuTA complex will have a greater effect on DAOY cell viability and Survivin expression than TA. We also hypothesize that Survivin knock-down will correlate with decrease in DAOY cell viability. Methods: Medulloblastoma cell line(DAOY) was treated with TA or CuTA(0, 5, 10, 20, 40, and 80 µM) for 24h, to determine the ic50 value. Cell viability was assessed using CellTiter-Glo reagent. Survivin protein levels were determined by Western blot analysis. Effect of Survivin knockdown on viability was assessed by treating cells with siRNA. Results: DAOY cells experienced a greater decrease in cell viability when treated with CuTA compared to TA. This correlated with decreased Survivin protein expression. Survivin knock-down with siRNA resulted in a 75% decrease in viability at 72h. Conclusion: Cu-TA is more efficacious in decreasing proliferation of DAOY cells compared to TA. This effect could be mediated by the increased inhibition of Survivin expression. Since Survivin is involved in drug resistance, Cu-TA could be combined with various chemotherapeutic reagents in future experiments to gain a better understanding of its potential in combination therapy.