Peroxisome proliferator-activated receptor delta as a molecular target to regulate lung cancer cell growth.
It has been assumed that prostaglandin (PG)I2 signaling contributes to the negative growth control of lung cancer cells; however, the mechanism remains unresolved. PGI2 functions through a cell surface G protein-coupled receptor (prostaglandin I2-binding receptor, IP) and also exerts an effect by interacting with a nuclear hormone receptor, peroxisome proliferator-activated receptor delta (PPARdelta). We found that PPARdelta was a key molecule of PGI2 signaling to give negative growth control of lung cancer cells (A549), using carbarprostacyclin, a PGI2 agonist for IP and PPARdelta, and L-165041, a PPARdelta agonist. Furthermore, PPARdelta-induced cell growth control was reinforced by the inhibition of cyclooxygenase. These results suggest that PPARdelta activation under the suppression of PG synthesis is important to regulate lung cancer cell growth.
Department of Food Science Research for Health, National Institute of Health and Nutrition, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8636, Japan.
Keiko
K
Fukumoto
Yoshihisa
Y
Yano
Nantiga
N
Virgona
Hiromi
H
Hagiwara
Hiromi
H
Sato
Hironobu
H
Senba
Kazuyuki
K
Suzuki
Ryuji
R
Asano
Kazuhiko
K
Yamada
Tomohiro
T
Yano
D017209:Apoptosis; D015536:Down-Regulation; D011464:Epoprostenol / Q000819:agonists / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D047494:PPAR delta / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000494:pharmacology; D044006:Receptors, Epoprostenol / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D047494:PPAR delta; D034741:RNA, Small Interfering; D044006:Receptors, Epoprostenol; D011464:Epoprostenol