Abstract
Furano‐1,2‐naphthoquinone (FNQ), prepared from 2‐hydroxy‐1,4‐naphthoquinone and chloroacetaldehyde in an efficient one‐pot reaction, exhibits an anti‐carcinogenic effect. FNQ exerted anti‐proliferative activity with the G~2~/M cell cycle arrest and apoptosis in A549 cells. FNQ‐induced G~2~/M arrest was correlated with a marked decrease in the expression levels of cyclin A and cyclin B, and their activating partner cyclin‐dependent kinases (Cdk) 1 and 2 with concomitant induction of p53, p21, and p27. FNQ‐induced apoptosis was accompanied with Bax up‐regulation and the down‐regulation of Bcl‐2, X‐linked inhibitor of apoptosis (XIAP), and survivin, resulting in cytochrome c release and sequential activation of caspase‐9 and caspase‐3. Western blot analysis revealed that FNQ suppressed EGFR phosphorylation and JAK2, STAT3, and STAT5 activation, but increased in activation of p38 MAPK and c‐Jun NH2‐terminal kinase (JNK) stress signal. The combined treatment of FNQ with AG1478 (a specific EGFR inhibitor) significantly enhanced the G~2~/M arrest and apoptosis, and also led to up‐regulation in Bax, p53, p21, p27, release of mitochondrial cytochrome c, and down‐regulation of Bcl‐2, XIAP, survivin, cyclin A, cyclin B, Cdk1, and Cdk2 in A549 cells. These findings suggest that FNQ‐mediated cytotoxicity of A549 cell related with the G~2~/M cell cycle arrest and apoptosis via inactivation of EGFR‐mediated signaling pathway. Copyright © 2010 John Wiley & Sons, Ltd.