title: 2-Amino-1,3,4-thiadiazole derivative (FABT) inhibits the extracellular signal-regulated kinase pathway and induces cell cycle arrest in human non-small lung carcinoma cells.
abstract: The anticancer potential of 2-amino-1,3,4-thiadiazole compounds has been documented by in vitro and in vivo studies. In our previous research, we described the synthesis as well as the antiproliferative and neuroprotective activities of 2-(4-fluorophenyloamino)-5-(2,4-dihydroxyphenyl)-1,3,4-thiadiazole (FABT). The aim of the present study was to investigate the molecular mechanisms involved in FABT-induced growth inhibition in A549 lung carcinoma cells. Western blotting analysis revealed that FABT inhibited the activation of the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway, and Real-time PCR analysis showed no changes in the expression of P44ERK1 and CREB1 genes. Furthermore, FABT induced cell cycle arrest in the GO/G1 phase and enhanced p27/Kip1 expression. Our results suggest that FABT acts by inhibiting ERK1/2 pathway and cell cycle progression through G1 into S phase in A549 cells. Further studies are needed to completely explain the molecular mechanisms of anticancer action of this 2-aminothiadiazole derivative.
authors.affiliation: Department of Medical Biology, Institute of Rural Health, Lublin, Poland. goskazyla@poczta.onet.pl
authors.forename: M
authors.initials: M
authors.lastname: Juszczak
authors.forename: J
authors.initials: J
authors.lastname: Matysiak
authors.forename: M
authors.initials: M
authors.lastname: Szeliga
authors.forename: P
authors.initials: P
authors.lastname: Pożarowski
authors.forename: A
authors.initials: A
authors.lastname: Niewiadomy
authors.forename: J
authors.initials: J
authors.lastname: Albrecht
authors.forename: W
authors.initials: W
authors.lastname: Rzeski
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D045744:Cell Line, Tumor; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008958:Models, Molecular; D013830:Thiadiazoles / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D013830:Thiadiazoles; D050760:Cyclin-Dependent Kinase Inhibitor p27; C010852:2-amino-1,3,4-thiadiazole; D048049:Extracellular Signal-Regulated MAP Kinases