Epidermal growth factor receptor (EGFR) is one of the important protein tyrosine kinases (PTKs), whose blockade by tyrosine kinase inhibitors (TKIs) has been introduced in the treatment of advanced non-small-cell lung cancers (NSCLCs). However, intrinsic and acquired resistance to the clinically used erlotinib or gefitinib leads to poor overall prognosis. The novel EGFR-TKI will provide alternative choices in NSCLC treatment and might be beneficial. We have previously reported the design and synthesis of a novel class of PTK inhibitors featuring the N-(2-oxo-1,2-dihydro-quinolin-3-ylmethyl)-thiourea framework. In this study, we examined the antitumor effect of compound 5a (DC27) in a panel of human lung carcinoma cell lines. The results of a bromodeoxyurdine (BrdU) incorporation assay revealed that cell proliferation was inhibited in a dose-dependent manner, with an IC50 of 2.5–12.9 µM, similar to gefitinib (1.1–15.6 µM). DC27 induced G₀/G1 arrest of cell cycle and apoptosis as tested by flow cytometry. DC27 markedly reduced tyrosine phosphorylation of EGFR and inhibited activation of Erk1/2 and AKT, two key downstream effectors of proliferation. In conclusion, DC27 has potent in vitro cytotoxicity against human lung carcinoma cells, possibly mediated by induction of apoptosis and cell cycle arrest in G₀/G1 phase.

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