NDLI: Anticancer activity of tolfenamic acid in medulloblastoma: a preclinical study

Content Provider	Springer Nature Link
Author	Eslin, Don Lee, Chris Sankpal, Umesh T. Maliakal, Pius Sutphin, Robert M. Abraham, Liz Basha, Riyaz
Copyright Year	2013
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.
Starting Page	2781
Ending Page	2789
Page Count	9
File Format	PDF
ISSN	10104283
Journal	Tumor Biology
Volume Number	34
Issue Number	5
e-ISSN	14230380
Language	English
Publisher	Springer Netherlands
Publisher Date	2013-05-18
Publisher Place	Dordrecht
Access Restriction	Subscribed
Subject Keyword	Pediatric brain tumors Medulloblastoma NSAID Survivin Transcription factors Sp1 Cancer Research
Content Type	Text
Resource Type	Article
Subject	Medicine Cancer Research

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