Reports about the anti-cancer activities of curcumin are accumulating. However, its effect on human large cell carcinoma NCI-H460 cells has never been scrutinized. In this study, we used curcumin to treat human non-small cell lung cancer cells (NCI-H460) to determine its anti-cancer activity. Various concentrations of curcumin were added to NCI-H460 cells for different durations in vitro and the subsequent changes in cell morphologies, viabilities, cell cycles, intracellular proteins and mRNA expressions were investigated. We found curcumin, when over 20 μM in concentration, induced NCI-H460 cell apoptosis and morphologic changes in a dose-dependent manner. After curcumin treatment, Bax and Bad were up-regulated, Bcl-2, Bcl-xL and XIAP were down-regulated. In addition, reactive oxygen species (ROS), cytoplasmic calcium and endoplasmic reticulum stress were increased in NCI-H460 cells after treatment with curcumin. These signals led to mitochondrial membrane potential decrease and culminated in caspase-3 activation. Apoptosis could also be induced through Fas-caspase-8 (extrinsic) pathway. The cell death induced by curcumin could be significantly reversed by adding ROS or caspase 8 inhibitors. NCI-H460 cells tended to be arrested at G2/M cell cycle stage after curcumin treatment. Down-regulation of cyclin-depedent kinase 1 by curcumin may be involved in the mechanism of such an arrest. In conclusion, curcumin exerts its anti-cancer effects on lung cancer NCI-H460 cells through apoptosis or cell cycle arrest. Curcumin is potentially an anti-cancer therapy for human large cell carcinoma of lung.
