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Tolfenamic acid enhances pancreatic cancer cell and tumor response to radiation therapy by inhibiting survivin protein expression.

Publication ,  Journal Article
Konduri, S; Colon, J; Baker, CH; Safe, S; Abbruzzese, JL; Abudayyeh, A; Basha, MR; Abdelrahim, M
Published in: Mol Cancer Ther
March 2009

Survivin is overexpressed in most human cancers, including pancreatic adenocarcinoma. Expression of survivin is regulated by specificity protein (Sp) proteins and related to resistance to radiation therapy. Tolfenamic acid induces Sp protein degradation in several cancer cell lines. The purpose of this study is to investigate whether tolfenamic acid inhibits survivin expression and sensitizes pancreatic cancer cells/tumor to radiotherapy. Panc1 and L3.6pl cells have been used to study the effect of radiation on survivin expression and to investigate the efficacy of tolfenamic acid in enhancing the response to radiation therapy. In addition, an orthotopic model for human pancreatic cancer has been used to confirm the efficacy of tolfenamic acid to enhance tumor response to radiation in vivo. Pancreatic cancer cell lines express variable levels of survivin mRNA/protein, which correlate with their radiosensitivity. Radiation increased survivin promoter activity and protein expression in Panc1 and L3.6pl cells and tolfenamic acid inhibited both constitutive and radiation-induced survivin protein expression and enhanced the response of pancreatic cancer cells to radiation therapy. In vivo studies show that tolfenamic acid enhanced the radiation-induced apoptosis associated with decreased survivin expression in tumors and this correlates with the enhanced response of these tumors to the radiation. Thus, tolfenamic acid significantly enhances pancreatic cancer cells/tumor response to radiation therapy. The underlying mechanism includes tolfenamic acid-induced degradation of Sp proteins, which in tumor decreases expression of the Sp-dependent antiapoptotic protein survivin. These preclinical data suggest that tolfenamic acid has the potential to increase the response of pancreatic adenocarcinoma to radiation therapy.

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Published In

Mol Cancer Ther

DOI

ISSN

1535-7163

Publication Date

March 2009

Volume

8

Issue

3

Start / End Page

533 / 542

Location

United States

Related Subject Headings

  • ortho-Aminobenzoates
  • Xenograft Model Antitumor Assays
  • Tumor Cells, Cultured
  • Survivin
  • Radiation-Sensitizing Agents
  • Radiation Tolerance
  • Promoter Regions, Genetic
  • Pancreatic Neoplasms
  • Oncology & Carcinogenesis
  • Microtubule-Associated Proteins
 

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Konduri, S., Colon, J., Baker, C. H., Safe, S., Abbruzzese, J. L., Abudayyeh, A., … Abdelrahim, M. (2009). Tolfenamic acid enhances pancreatic cancer cell and tumor response to radiation therapy by inhibiting survivin protein expression. Mol Cancer Ther, 8(3), 533–542. https://doi.org/10.1158/1535-7163.MCT-08-0405
Konduri, Santhi, Jimmie Colon, Cheryl H. Baker, Stephen Safe, James L. Abbruzzese, Ala Abudayyeh, Md Riyaz Basha, and Maen Abdelrahim. “Tolfenamic acid enhances pancreatic cancer cell and tumor response to radiation therapy by inhibiting survivin protein expression.Mol Cancer Ther 8, no. 3 (March 2009): 533–42. https://doi.org/10.1158/1535-7163.MCT-08-0405.
Konduri S, Colon J, Baker CH, Safe S, Abbruzzese JL, Abudayyeh A, et al. Tolfenamic acid enhances pancreatic cancer cell and tumor response to radiation therapy by inhibiting survivin protein expression. Mol Cancer Ther. 2009 Mar;8(3):533–42.
Konduri, Santhi, et al. “Tolfenamic acid enhances pancreatic cancer cell and tumor response to radiation therapy by inhibiting survivin protein expression.Mol Cancer Ther, vol. 8, no. 3, Mar. 2009, pp. 533–42. Pubmed, doi:10.1158/1535-7163.MCT-08-0405.
Konduri S, Colon J, Baker CH, Safe S, Abbruzzese JL, Abudayyeh A, Basha MR, Abdelrahim M. Tolfenamic acid enhances pancreatic cancer cell and tumor response to radiation therapy by inhibiting survivin protein expression. Mol Cancer Ther. 2009 Mar;8(3):533–542.

Published In

Mol Cancer Ther

DOI

ISSN

1535-7163

Publication Date

March 2009

Volume

8

Issue

3

Start / End Page

533 / 542

Location

United States

Related Subject Headings

  • ortho-Aminobenzoates
  • Xenograft Model Antitumor Assays
  • Tumor Cells, Cultured
  • Survivin
  • Radiation-Sensitizing Agents
  • Radiation Tolerance
  • Promoter Regions, Genetic
  • Pancreatic Neoplasms
  • Oncology & Carcinogenesis
  • Microtubule-Associated Proteins