Evaluation of preventive and therapeutic activity of novel non-steroidal anti-inflammatory drug, CG100649, in colon cancer: Increased expression of TNF-related apoptosis-inducing ligand receptors enhance the apoptotic response to combination treatment with TRAIL

  • Authors:
    • Jong Kyu Woo
    • Ju-Hee Kang
    • Yeong-Su Jang
    • Seonggu Ro
    • Joong Myung Cho
    • Hwan-Mook Kim
    • Sang-Jin Lee
    • Seung Hyun Oh
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  • Published online on: February 10, 2015     https://doi.org/10.3892/or.2015.3793
  • Pages: 1947-1955
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Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs) have been suggested as the potential new class of preventive or therapeutic antitumor agents. The aim of the present study was to evaluate the antitumor activity of the novel NSAID, CG100649. CG100649 is a novel NSAID dual inhibitor for COX-2 and carbonic anhydrase (CA)-I/-II. In the present study, we investigated the alternative mechanism by which CG100649 mediated suppression of the colon cancer growth and development. The anchorage‑dependent and -independent clonogenic assay showed that CG100649 inhibited the clonogenicity of human colon cancer cells. The flow cytometric analysis showed that CG100649 induced the G2/M cell cycle arrest in colon cancer cells. Animal studies showed that CG100649 inhibited the tumor growth in colon cancer xenograft in nude mice. Furthermore, quantitative PCR and FACS analysis demonstrated that CG100649 upregulated the expression of TNF-related apoptosis-inducing ligand (TRAIL) receptors (DR4 and DR5) but decreased the expression of decoy receptors (DcR1 and DcR2) in colon cancer cells. The results showed that CG100649 treatment sensitized TRAIL‑mediated growth suppression and apoptotic cell death. The combination treatment resulted in significant repression of the intestinal polyp formation in APCmin/+ mice. Our data clearly demonstrated that CG100649 contains preventive and therapeutic activity for colon cancer. The present study may be useful for identification of the potential benefit of the NSAID CG100649, for the achievement of a better treatment response in colon cancer.
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April-2015
Volume 33 Issue 4

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Woo JK, Kang J, Jang Y, Ro S, Cho JM, Kim H, Lee S and Oh SH: Evaluation of preventive and therapeutic activity of novel non-steroidal anti-inflammatory drug, CG100649, in colon cancer: Increased expression of TNF-related apoptosis-inducing ligand receptors enhance the apoptotic response to combination treatment with TRAIL. Oncol Rep 33: 1947-1955, 2015.
APA
Woo, J.K., Kang, J., Jang, Y., Ro, S., Cho, J.M., Kim, H. ... Oh, S.H. (2015). Evaluation of preventive and therapeutic activity of novel non-steroidal anti-inflammatory drug, CG100649, in colon cancer: Increased expression of TNF-related apoptosis-inducing ligand receptors enhance the apoptotic response to combination treatment with TRAIL. Oncology Reports, 33, 1947-1955. https://doi.org/10.3892/or.2015.3793
MLA
Woo, J. K., Kang, J., Jang, Y., Ro, S., Cho, J. M., Kim, H., Lee, S., Oh, S. H."Evaluation of preventive and therapeutic activity of novel non-steroidal anti-inflammatory drug, CG100649, in colon cancer: Increased expression of TNF-related apoptosis-inducing ligand receptors enhance the apoptotic response to combination treatment with TRAIL". Oncology Reports 33.4 (2015): 1947-1955.
Chicago
Woo, J. K., Kang, J., Jang, Y., Ro, S., Cho, J. M., Kim, H., Lee, S., Oh, S. H."Evaluation of preventive and therapeutic activity of novel non-steroidal anti-inflammatory drug, CG100649, in colon cancer: Increased expression of TNF-related apoptosis-inducing ligand receptors enhance the apoptotic response to combination treatment with TRAIL". Oncology Reports 33, no. 4 (2015): 1947-1955. https://doi.org/10.3892/or.2015.3793