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 | Zendy

Jong Kyu Woo | Zendy; JuHee Kang | Zendy; YeongSu Jang | Zendy; Seonggu Ro | Zendy; Joong Myung Cho | Zendy; HwanMook Kim | Zendy; Sangjin Lee | Zendy; Seung Hyun Oh | Zendy

Open Access

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

Author(s) -

Jong Kyu Woo,

JuHee Kang,

YeongSu Jang,

Seonggu Ro,

Joong Myung Cho,

HwanMook Kim,

Sangjin Lee,

Seung Hyun Oh

Publication year - 2015

Publication title -

oncology reports

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 1.094

H-Index - 96

eISSN - 1791-2431

pISSN - 1021-335X

DOI - 10.3892/or.2015.3793

Subject(s) - apoptosis , clonogenic assay , colorectal cancer , cancer , oncogene , cancer research , cell cycle , tumor necrosis factor alpha , medicine , molecular medicine , pharmacology , cancer cell , receptor , immunology , biology , biochemistry

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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