Anticancer activity of tolfenamic acid in medulloblastoma: a preclinical study

• DOI: 10.1007/s13277-013-0836-6
• Publication Date: 2013-05-17T06:20:31Z
• Authors: Don Eslin; Chris Lee; Umesh T. Sankpal; Pius Maliakal; Robert M. Sutphin; Liz Abraham; Riyaz Basha
• Keywords: Survivin; Viability assay

Medulloblastoma (MB) is the most common malignancy in children arising brain. Morbidities associated with intensive therapy are serious concerns treating MB. Our aim was to identify novel targets and agents less toxicity for Specificity protein 1 (Sp1) transcription factor regulates several genes involved cell proliferation survival including survivin, an inhibitor of apoptosis protein. We previously showed that tolfenamic acid (TA), a nonsteroidal anti-inflammatory drug, inhibits neuroblastoma growth by targeting Sp1. investigated anticancer activity TA using human MB lines mouse xenograft model. DAOY D283 cells were treated vehicle (dimethyl sulfoxide) or (5-50 μg/ml), viability measured at 1-3 days posttreatment. inhibited time- dose-dependent manner. (10 effect on measured. Apoptosis analyzed flow cytometry (annexin V staining), caspase 3/7 determined Caspase-Glo kit. The expression Sp1, cleaved poly(ADP-ribose) polymerase (c-PARP), survivin Western blot analysis. Sp1 upregulated c-PARP. Athymic nude mice subcutaneously injected (50 mg/kg, three times per week) 4 weeks. caused decrease ~40 % tumor weight volume. inhibition accompanied tissue. These preclinical data demonstrate acts as agent potentially survivin.