Abstract 4075: Tolfenamic Acid Inhibits Prostate Cancer Cells Growth and Tumor Development in Orthotopic Mice Academic Article uri icon


  • Abstract Introduction: Transcription factors, Specificity proteins (Sp) play a critical role in growth and metastasis of cancer and there is clear evidence that Sp1 expression is a negative prognostic factor for survival in some cancer patients. Sp proteins regulate the expression of several genes, including PSA gene and c-Met which are associated with prostate cancer. Nonsteroidal anti-inflammatory drug, tolfenamic acid (TA) induces the degradation of specific Sp proteins (Sp1, Sp3 and Sp4) which play critical role in tumor growth and metastasis. Sp proteins also regulate the expression of survivin, a member of inhibitor of apoptosis gene family which is associated with resistance to chemotherapy and radiotherapy in several cancers. We have evaluated the anti-cancer activity of TA in prostate cancer. Methods and Results: Human prostate cancer cells (PC-3, DU-145 and LNcaP) were grown in the presence of DMSO (vehicle) or various concentrations (25, 50 and 100 M) of TA and cell number and viability were measured at 24, 48, and 72 h post-treatment. Cell viability was measured using Cell Titr Glo kit (Promega) and the experiments were performed in triplicate. Cell lysates were prepared from the cells exposed to DMSO or 50 M TA for 48 h and evaluated the expression of Sp proteins (Sp1, Sp3 and Sp4), and c-Met through Western blot analysis. For in vivo studies nude mice were injected with PC-3 Luc cells into the right prostate. Treatment (vehicle or 50 mg/kg TA/2 days) was initiated after one week and tumor growth was continuously monitored through Kodak imaging system. 4 weeks after the treatment tumors were isolated, measured and processed for immunohistochemistry to analyze the expression of Sp proteins and c-Met. In vitro studies show a significant decrease in the cell proliferation and viability and these results are dose and time dependent in all the cell lines. Furthermore, TA treatment for 48 h significantly decreased the expression of Sp1, Sp3 and c-Met in PC-3 cells. In vivo studies revealed that TA significantly decreased the tumor weight and volume which was associated with a low expression of Sp1, Sp3 and c-Met in tumor sections as evaluated by immunohistochemistry. Conclusion: Targeting key transcription factors such as Sp proteins using a small molecule compound, TA is a new strategy for the treatment of prostate cancer and our results are very crucial in the development of a safe, cost effective drug for the treatment of this devastating disease. Studies to test the effect of TA on critical genes associated with prostate cancer and TA's impact on developing higher response to radiation therapy are underway. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4075.

published proceedings

  • Cancer Research

author list (cited authors)

  • Mahammad, R. B., Madero-Visbal, R., Baker, C. H., Colon, J., Safe, S., Abudayyeh, A., & Abdelrahim, M.

citation count

  • 1

publication date

  • April 2010