TY - JOUR
T1 - A novel indole compound, AWT-489, inhibits prostaglandin D 2-induced CD55 expression by acting on DP prostanoid receptors as an antagonist in LS174T human colon cancer cells
AU - Oyama, Satomi
AU - Fujino, Hiromichi
AU - Yamazaki, Risa
AU - Okura, Iori
AU - Regan, John W.
AU - Awata, Atsuko
AU - Arai, Takayoshi
AU - Murayama, Toshihiko
N1 - Funding Information:
This research was supported in part by a Grant-in-aid for Scientific Research (22590079 and 25460091) from the Ministry of Education, Culture, Sports, Science and Technology, Japan , and a Start-up COE program (Director; Dr. Takayoshi Arai) from Chiba University, Japan.
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
KW - AWT-489
KW - CD55
KW - DP receptor antagonist
KW - Indole
KW - LS174T cells
UR - http://www.scopus.com/inward/record.url?scp=84888237637&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84888237637&partnerID=8YFLogxK
U2 - 10.1016/j.abb.2013.10.023
DO - 10.1016/j.abb.2013.10.023
M3 - Article
C2 - 24239863
AN - SCOPUS:84888237637
SN - 0003-9861
VL - 541
SP - 21
EP - 29
JO - Archives of Biochemistry and Biophysics
JF - Archives of Biochemistry and Biophysics
IS - 1
ER -