Chou J.-Y.Lai S.-Y.Pan S.-L.Jow G.-M.Chern J.-W.JIH-HWA GUH2021-06-022021-06-02200362952https://www.scopus.com/inward/record.uri?eid=2-s2.0-0038005576&doi=10.1016%2fS0006-2952%2803%2900254-5&partnerID=40&md5=3f84221e9cab2d550657bc1c1327e915https://scholars.lib.ntu.edu.tw/handle/123456789/564881In this study, we have synthesized several compounds and examined their cytotoxic effects on human non-small cell lung cancer A549 cells. We found that GO-13 ((E,E)-2,5-bis[4-(3-dimethyl-aminopropoxy)styryl]-1,3,4-thiadiazole) is the most effective one by the MTT assay. Furthermore, the GO-13-induced apoptotic reaction was identified based on several criteria, such as negative release reaction of lactate dehydrogenase and positive labeling of annexin V and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) techniques. GO-13 induced the apoptosis in A549 cells in a concentration- and time-dependent manner. The data demonstrate that the regulations of p38 mitogen-activated protein kinase and protein kinase C was not involved in the GO-13-mediated mechanism. However, GO-13 significantly induced a down-regulation of Bcl-XL expression in a short-term treatment (less than 3hr), whereas stimulated up-regulation of Bax expression in a long-term treatment (24hr) indicating their involvement in GO-13 action. GO-13-mediated apoptosis is also positively correlated with the increase in caspase-3 activity. Worth noting is the fact that GO-13 did not modify the phosphorylation level of Akt/protein kinase B (PKB) until a 24-hr exposure was carried out indicating that the inhibition of Akt/PKB activation was involved in the late-phase apoptosis. Besides the anticancer activity, GO-13 also showed equivalent anti-angiogenic activity in the nude mice angiogenesis model. In summary, we conclude that GO-13 is the most effective anticancer compound in our screening tests. It induced the early-phase apoptosis in A549 cells via the Bcl-XL down-regulation, and that of the late-phase through up-regulation of Bax expression as well as inhibition of Akt/PKB activation. ? 2003 Elsevier Science Inc. All rights reserved.Apoptosis; Bax; Bcl-XL; Phosphoinositide 3-kinase; Thiadiazole[SDGs]SDG32,5 bis[4 (3 dimethylaminopropoxy)styryl] 1,3,4 thiadiazole; caspase 3; DNA nucleotidylexotransferase; go 13; lactate dehydrogenase; lipocortin 5; mitogen activated protein kinase; protein Bax; protein bcl xl; protein kinase B; protein kinase C; thiadiazole derivative; unclassified drug; angiogenesis; antineoplastic activity; apoptosis; article; cancer cell culture; concentration response; cytotoxicity; down regulation; drug synthesis; enzyme activity; human; human cell; lung non small cell cancer; nick end labeling; nude mouse; priority journal; protein expression; protein phosphorylation; upregulationjournal article10.1016/S0006-2952(03)00254-5128183712-s2.0-0038005576