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Abstract. Bronchial asthma is a chronic inflammatory disorder of the airways, in which inflammation causes bronchial hyper-responsiveness and flow limitation in the presence of various stimuli. Pulmonary function in asthmatic patients frequently deteriorates between midnight and early morning, which has suggested a role for chronotherapy. Although relationships between bronchial asthma and the function of clock genes remain unclear, some medications given for asthma such as glucocorticoids or β 2 -adrenoceptor agonists may influence clock genes in vivo. In our studies of clock gene mRNA expressions in human bronchial epithelial cells in vitro and peripheral blood cells in vivo, we demonstrated that glucocorticoid or β 2 -adrenoceptor agonist treatment strongly induced human Per1 mRNA expression both in vitro and in vivo. Human peripheral blood cells provide a useful indication of peripheral clock gene mRNA expression in vivo.

Cell migration is essential for invasive and metastatic phenotypes of cancer cells. Potential chemopreventive agents of cancer-sulindac sulfide, caffeic acid phenethyl ester (CAPE), curcumin, and (+)-catechin-have been reported to interfere with several types of intracellular signaling. In this study, we examined the effects of these agents on transforming growth factorb(TGF-b)-induced motility and Akt phosphorylation in A549 cells. Judged by gold particle phagokinesis assay, sulindac sulfide, CAPE, and curcumin suppressed the motility of A549 cells promoted by TGF-b. LY294002, a specific inhibitor of phosphatidylinositol 3-kinase (PI3K)/Akt signaling, also suppressed TGF-b-induced motility and Akt phosphorylation. Sulindac sulfide and CAPE, but not curcumin, suppressed TGF-b-induced Akt phosphorylation. We conclude that sulindac sulfide and CAPE suppress the motility promoted by TGF-b in lung adenocarcinoma cells through the suppression of Akt. Our observations raise the possibility that these agents, except for (+)-catechin, can be applied not only as chemopreventive agents but also as anti-metastatic therapy.Keywords A549 AE Akt AE TGF-b AE Sulindac sulfide AE Caffeic acid phenethyl ester Abbreviations CAPE Caffeic acid phenethyl ester AE TGF-b Transforming growth factor-b AE FAK Focal adhesion kinase AE MMP-2 Matrix metalloproteinase-2

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