A novel indole compound, AWT-489, inhibits prostaglandin D2-induced CD55 expression by acting on DP prostanoid receptors as an antagonist in LS174T human colon cancer cells
| Autor: | Risa Yamazaki, Iori Okura, Satomi Oyama, Toshihiko Murayama, John W. Regan, Atsuko Awata, Hiromichi Fujino, Takayoshi Arai |
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| Rok vydání: | 2014 |
| Předmět: |
Indole Compound
Indoles Carcinogenesis Colorectal cancer Receptors Prostaglandin Biophysics Pharmacology Biology Biochemistry Dinoprostone chemistry.chemical_compound Cell Line Tumor Cyclic AMP medicine Humans RNA Messenger Receptors Immunologic Receptor Molecular Biology Indole test CD55 Antigens Prostaglandin D2 Hydantoins Antagonist Prostanoid medicine.disease Complement system Gene Expression Regulation Neoplastic chemistry Drug Design Colonic Neoplasms |
| Zdroj: | Archives of Biochemistry and Biophysics. 541:21-29 |
| ISSN: | 0003-9861 |
| DOI: | 10.1016/j.abb.2013.10.023 |
| Popis: | Indoles are composed of a common core structure, the indole ring, and are widely used as pharmaceuticals and their precursors. In this study, a newly composed relatively small indole compound, AWT-489 was examined to find a novel specific antagonist for DP receptors; the cognate receptors for prostaglandin D2 (PGD2), to prevent colon cancer malignancy. Here we showed that AWT-489 antagonized DP receptor-mediated cyclic AMP formation, and expression of CD55, an inhibitor of the complement system that correlates with poor survival in patients with colorectal cancer, in LS174T human colon cancer cells. Interestingly, unlike a popular indole compound, indomethacin, AWT-489 did not act on the cyclooxygenases as a non-steroidal anti-inflammatory drug. Moreover, AWT-489 exhibited a better inhibitory effect than that of the well-used DP receptor antagonist, BWA868C when a dose close to the physiological concentration of PGD2 was used. These results suggest that AWT-489 can act as a novel human DP receptor antagonist to reduce the expression of CD55 in LS174T human colon cancer cells. We believe that AWT-489 has potential as a lead compound for designing a new DP receptor antagonist that may help improve PGD2-related diseases, especially colon cancer in the near future. |
| Databáze: | OpenAIRE |
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