Curcumin induces apoptosis in human non-small cell lung cancer NCI-H460 cells through ER stress and caspase cascade- and mitochondria-dependent pathways

Division of Critical Care Medicine, Department of Internal Medicine, Changhua Christian Hospital, Changhua 500, Taiwan, ROC.
Anticancer research (Impact Factor: 1.83). 06/2010; 30(6):2125-33.
Source: PubMed


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-X(L) and XIAP were down-regulated. In addition, reactive oxygen species (ROS), intracellular Ca(2+) 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 (Delta Psi(m)) 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 G(2)/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.

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    • "enhance bioavailability. Overwhelmingly, mechanisms of action reported for the antitumor efficacy of curcumin in lung cancer cells are via mitochondrial-mediated cell death elicited by an increase in the Bax:B cell lymphoma-2 ratio or by an increase in intracellular reactive oxygen species (ROS) (Chanvorachote et al., 2009; Pongrakhananon et al., 2010; Saha et al., 2010; Wu et al., 2010; Wang et al., 2011, 2013b; Sahoo et al., 2012; Yang et al., 2012a,b; Li et al., 2013; Liu et al., 2013; Xiao et al., 2013; Chen et al., 2014). Migration and invasive capacity of lung cancer cells may be further decreased by inhibition of matrix metalloprotease expression, decreased nuclear factor-kB, EGFR, Akt, signal transducer and activator of transcription 3, and Cdc42 signaling (Chen et al., 2004, 2012, 2014; Lee et al., 2005; Lin et al., 2009, 2012; Puliyappadamba et al., 2010; Kaushik et al., 2012; Liu et al., 2013; Yamauchi et al., 2014; Zhou et al., 2013a; Li et al., 2014b). "
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    • "Curcumin (diferuloylmethane), the dietary polyphenol constituent of the perennial herb Curcuma longa (popularly known as turmeric), exhibits wide range of bioactivities including antioxidant , anti-inflammatory, anti-cancer, anti-angiogenic and antimicrobial properties [1]. Curcumin's chemopreventive characteristics , in particular, have been demonstrated against a wide range of cancers including bladder [2], cervical [3], lung [4] [5], pancreatic [6], colorectal [7] cancers, etc. Despite curcumin's remarkable nontoxic nature [7], extremely low water solubility and poor bioavailability are impeding its effective clinical use [8] [9]. "
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