2-(4-fluorophenylamino)-5-(2-4-dihydroxyphenyl)-1-3-4-thiadiazole and Carcinoma--Non-Small-Cell-Lung

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.

Topics: Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Cell Cycle Checkpoints; Cell Line, Tumor; Cyclin-Dependent Kinase Inhibitor p27; Extracellular Signal-Regulated MAP Kinases; Gene Expression Regulation, Neoplastic; Humans; Lung Neoplasms; MAP Kinase Signaling System; Models, Molecular; Thiadiazoles