Tumor Biology

, Volume 34, Issue 5, pp 2781–2789

Anticancer activity of tolfenamic acid in medulloblastoma: a preclinical study

Research Article

DOI: 10.1007/s13277-013-0836-6

Cite this article as:
Eslin, D., Lee, C., Sankpal, U.T. et al. Tumor Biol. (2013) 34: 2781. doi:10.1007/s13277-013-0836-6

Abstract

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

Keywords

Pediatric brain tumors Medulloblastoma NSAID Survivin Transcription factors Sp1 

Supplementary material

13277_2013_836_MOESM1_ESM.pdf (147 kb)
ESM 1(PDF 147 kb)

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2013

Authors and Affiliations

  • Don Eslin
    • 1
    • 2
  • Chris Lee
    • 1
  • Umesh T. Sankpal
    • 1
  • Pius Maliakal
    • 1
  • Robert M. Sutphin
    • 1
    • 2
  • Liz Abraham
    • 1
  • Riyaz Basha
    • 1
  1. 1.MD Anderson Cancer Center OrlandoOrlandoUSA
  2. 2.Arnold Palmer Hospital for ChildrenOrlandoUSA

Personalised recommendations