RT Journal Article SR Electronic T1 Curcumin Induces Apoptosis in Human Non-small Cell Lung Cancer NCI-H460 Cells through ER Stress and Caspase Cascade- and Mitochondria-dependent Pathways JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 2125 OP 2133 VO 30 IS 6 A1 SHIN-HWAR WU A1 LIANG-WEN HANG A1 JAI-SING YANG A1 HUNG-YI CHEN A1 HUI-YI LIN A1 JO-HUA CHIANG A1 CHI-CHENG LU A1 JIUN-LONG YANG A1 TUNG-YUAN LAI A1 YANG-CHING KO A1 JING-GUNG CHUNG YR 2010 UL http://ar.iiarjournals.org/content/30/6/2125.abstract AB It has been reported that curcumin inhibited various types of cancer cells in vitro and in vivo. However, mechanisms of curcumin-inhibited cell growth and -induced apoptosis in human non-small cell lung cancer cells (NCI-H460) still remain unclear. In this study, NCI-H460 cells were treated with curcumin to determine its anticancer activity. Different concentrations of curcumin were used for different durations in NCI-H460 cells and the subsequent changes in the cell morphology, viability, cell cycle, mRNA and protein expressions were determined. Curcumin induced apoptotic morphologic changes in NCI-H460 cells 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), intracellular Ca2+ and endoplasmic reticulum (ER) stress were increased in NCI-H460 cells after exposure to curcumin. These signals led to a loss of mitochondrial membrane potential (ΔΨm) and culminated in caspase-3 activation. Curcumin-induced apoptosis was also stimulated through the FAS/caspase-8 (extrinsic) pathway and ER stress proteins, growth arrest- and DNA damage-inducible gene 153 (GADD153) and glucose-regulated protein 78 (GRP78) were activated in the NCI-H460 cells. Apoptotic cell death induced by curcumin was significantly reversed by pretreatment with ROS scavenger or caspase-8 inhibitor. Furthermore, the NCI-H460 cells tended to be arrested at the G2/M cell cycle stage after curcumin treatment and down-regulation of cyclin-dependent kinase 1 (CDK1) may be involved. In summary, curcumin exerts its anticancer effects on lung cancer NCI-H460 cells through apoptosis or cell cycle arrest.