A selection of in vitro data alluding to potential utility for curcumin in tertiary lung cancer chemoprevention strategies
| Year | Model | Observations | Refence |
|---|---|---|---|
| 2014 | PC-9, H1975, H1650 NSCLC cell lines | Curcumin increased cytotoxicity of erlotinib in erlotinib-resistant cell lines. It enhanced erlotinib-induced apoptosis, downregulated EGFR, p-EGFR, surviving, and inhibited NFκB activation in erlotinib-resistant cell lines. | Li et al., 2014a |
| 2014 | Large-cell lung carcinoma cell line 801D | Curcumin (10–60 μM) inhibits viability, EGFR and TGFβ1-induced migration, Rac1 protein expression, MMP2, and MMP9. | Chen et al., 2014 |
| 2013 | A549, H460, BEAS-2B cell lines | Synthetic monocarbonyl analog of curcumin (B85) inhibits proliferation and induces apoptosis via activation of endoplasmic reticulum stress-mediated pathway. | Liu et al., 2013 |
| 2013 | H460, A549 cell lines | Solid lipid nanoparticle curcumin inhibits growth and induces apoptosis with an IC50 4- to 5-fold lower than for native curcumin. | Wang et al., 2013b |
| 2013 | A549 cell line | Curcumin (5–40 μM) increases the Bax:Bcl-2 ratio, causing apoptosis via mitochondrial cytochrome c release. | Li et al., 2013 |
| 2013 | A549, IMP-90 (lung fibroblast) | Curcumin (50 and 100 μM) induces LC3-II resulting in autophagy. Concomitant increases in phosphorylation of AMPK and ACC observed. | Xiao et al., 2013 |
| 2014 | A549 cell line | Hydrazinobenzoylcurcumin (10–80 μM) induced autophagosome formation in a time- and dose-dependent manner, in conjunction with accumulation of LC3-II. | Zhou et al., 2014 |
| 2012 | A549 cell line | Curcumin sensitizes cells to redox-mediated apoptosis. Apoptosis is accompanied by decreased ratio of glutathione:oxidized glutathione and increased p38 MAPK phosphorylation. | Kaushik et al., 2012 |
| 2013 | A549, H1299, H460, PC9 cell lines | Curcumin (5–100 μM) augments erlotinib-induced apoptosis and increases IκB. | Yamauchi et al., 2014 |
| 2014 | A549, H460 cell lines | Curcumin (1–50 μM) causes growth inhibition via cell cycle arrest, mediated by increased p21 and p27 and decreased cyclin D1. An increase in FOXO1 is caused by curcumin-induced increase in ERK1/2 phosphorylation. | Li et al., 2014b |
| 2013 | A549 cell line | Curcumin-loaded nanoparticles demonstrated enhanced cytotoxicity compared with native curcumin. | Yin et al., 2013a |
| 2013 | A549 cell line | Curcumin analog 4-arylidene curcumin inhibits NFκB by acting as an irreversible deubiquitinase inhibitor of the 19S regulatory particle, and reactivates p53. | Zhou et al., 2013b |
| 2013 | A549 cell line | Curcumin nanoparticles (5–100 μM) inhibited TNFα-induced ICAM-1 expression and TNFα-induced ROS expression. | Yen et al., 2013 |
| 2013 | A549 and cisplatin-resistant A549 cell lines | (1E,4Z,6E)-5-Hydroxy-1-(4-hydroxy-3-methoxyphenyl)-7-(5-methylfuran-2-yl)hepta-1,4,6-trien-3-one (2a), a novel curcumin analog (1.56–100 μM), causes greater growth inhibition in cisplatin-resistant cells. This is accompanied by inhibition of thioredoxin reductase activity leading to intracellular ROS generation and induction of apoptosis. | Zhou et al., 2013a |
| 2012 | NCI-H446, NCI-H1688 small-cell lung cancer (SCLC) cell lines | Curcumin (15 μM) inhibits IL-6–induced proliferation, migration, and invasion of SCLC cells and causes G2N cell cycle arrest. Also inhibits IL-6–induced STAT3, JAK1,2, and 3 phosphorylation, and downregulates MMP2, MMP3, VEGF, survivin, Bcl-XL, and ICAM-1. | Yang et al., 2012a |
| 2012 | A549 and cisplatin-resistant A549 cell lines | Curcumin (10–40 μM) inhibits growth in cisplatin sensitive and resistant cell lines to a similar extent, but sensitizes resistant cells to apoptosis via caspase-3 activation. Curcumin inhibits HIF-1α and decreases p-glycoprotein levels. | Ye et al., 2012 |
| 2012 | A549, 95D, 901D, 95C, BEAS-2B cell lines | Curcumin (5–20 μM) inhibits migration and invasion of 801D cells, inhibits Cdc42 expression and Cdc42-regulated expression of invasion and metastasis genes (PAK1, cofilin). | Chen et al., 2012 |
| 2012 | AALE normal bronchoepithelial cells, H441 cells | Curcumin (1–50 μM) inhibits proliferation and STAT3 phosphorylation in both cell lines. | Alexandrow et al., 2012 |
| 2012 | NCI-H446 (SCLC) cell line | Curcumin causes apoptosis by mitochondrial-mediated pathways, inducing Bax expression and decreasing expression of Bcl-2 and Bcl-xL, concurrent with an increase in intracellular ROS. | Yang et al., 2012b |
| 2012 | A549, H1299 | Curcumin (2.5–40 μM) inhibits cell growth, which is synergistically enhanced when combined with small-molecule inhibitors against EGFR, IGF1R, FGFR, PI3K, and NFκB. | Lin et al., 2012 |
| 2011 | H460 | Curcumin analog (1E,4E)-1,5-bis(2,3-dimethoxyphenyl)penta-1,4-dien-3-one upregulates C/EBP homologous protein (CHOP) to stimulate the ER stress-mediated apoptotic pathway. | Wang et al., 2011 |
| 2011 | A549, H460, SPC-A1 | Bisdemethoxy (BDMC) and demethoxy curcumin (DMC) had greater hypomethylation effects than curcumin (20–100 μM). BDMC and DMC decreased hypomethylation in WIF-1 promoter resulting in restoration of WIF-1 protein levels. | Liu et al., 2011 |
| 2012 | NCI-H441, CCL-151 (normal fibroblast) cell lines | Curcumin analog 4-[3,5-bis(2-chlorobenzylidene-4-oxo-piperidine-1-yl)-4-oxo-2-butenoic acid] (CLEFMA) caused rapid depletion of glutathione:oxidized glutathione ratio and induction of ROS in cancer cells only. | Sahoo et al., 2012 |
| 2010 | A549 cell line | Curcumin downregulates miRNAs miR-186, 625, 576, 39, 9, let7e, and upregulates miRNAs miR-320, 26a, 16, 130a, 125b, 23a, 23b, let7i. | Zhang et al., 2010a |
| 2010 | A549, H1299 cell lines | Curcumin (10 μM, 2 h prior to nicotine induction) inhibits nicotine-induced phosphorylation of Akt, ERK1/2, JNK, and p38, and decreases protein levels of Cox2, cyclin D1, Bcl-2, and inhibitors of apoptosis. | Puliyappadamba et al., 2010 |
| 2010 | PC-9, A549 cell lines | Curcumin (25–50 μM) upregulated growth arrest and DNA damage inducible genes (GADD) 45 and 153, concomitant with upregulation of p21 and p27 and downregulation of Bcl-2. | Saha et al., 2010 |
| 2010 | H460 cell line | Curcumin (5–50 μM) promoted G2/M cell cycle arrest and induced caspase-3, -8, and -9 activity. Decreases in Bcl-2, Bcl-xL, and XIAP were observed in conjunction with increases in Bad, Bax, and FAS. | Wu et al., 2010 |
| 2010 | A549 and cisplatin-resistant A549 cell lines | Curcumin (10–50 μM) induces apoptosis in the drug-resistant cell line by downregulating miR-186. | Zhang et al., 2010b |
| 2010 | A549 cell line | Curcumin (5–40 μM) induces apoptosis by a mitochondrial-mediated mechanism leading to cleavage of caspases-3 and -9 and PARP. Ratio of Bax:Bcl-2 is significantly enhanced. | Chen et al., 2010b |
| 2010 | H460, BEAS-2B cell lines | Curcumin (0.25–5 μM) sensitizes lung cancer cells to anoikis-induced cell death via inhibition of Bcl-2 and ROS generation. | Pongrakhananon et al., 2010 |
| 2010 | A549 cells | Curcumin (20–40 μM) significantly downregulates eIF2α, eIF4E, and phospho-4E-BP1, and upregulates phospho-eIF2α and phospho-eIF4E. | Chen et al., 2010a |
| 2009 | A549 cells | Curcumin (10–20 μM) inhibits migration and invasion, and downregulates PI3K, PKC, VEGF, cjun-p, Ras, GRB2, MEKK3, FAK, MKK7, JNK, ERK, MMP2, MMP9, and RhoA. | Lin et al., 2009 |
| 2010 | A549 cells | Curcumin (10–50 μM) decreases the activity of the Pokemon promoter by preventing recruitment of its transcriptional activator, SP-1. | Cui et al., 2010 |
| 2009 | H460 cells | Curcumin (50–100 μM) reverses cisplatin resistance and enhances cisplatin-induced apoptosis by induction of intracellular ROS and proteosomal degradation of Bcl-2. | Chanvorachote et al., 2009 |
| 2008 | CL1-5 cells | Curcumin (1–20 μM) decreased invasion and migration associated with increased expression of the tumor suppressor HLJ-1. HJL-1 is transcriptionally upregulated following a curcumin-induced increase in binding of the transcription factor AP-1. | Chen et al., 2008 |
| 2008 | A549 cells | Curcumin (5–50 μM) prevented the IFNα-induced increase in NFκB by downregulating protein expression of its p50 and p65 subunits, leading to a consequential decrease in COX2 activity. | Lee et al., 2005 |
| 2005 | H520 cells | Curcumin (25 μM) enhanced the apoptotic response of vinorelbine. | Sen et al., 2005 |
| 2004 | CL1-5 cells | Curcumin (1–20 μM) inhibited invasion at low doses. Microarray analysis and protein verification revealed inhibition of NCAM, MMP14, and TOPO-IIa, and upregulation of heat shock protein family members. | Chen et al., 2004 |
AALE cells, tracheobronchio epithelial cell line; ACC, acetyl-CoA carboxylase; AMPK, 5′AMP-activated protein kinase; AP-1, activator protein-1; Bad, BCL2-associated agonist of cell death; Bcl-2, B cell lymphoma-2; COX2, cyclooxygenase-2; 4E-BP1, eukaryotic translation initiation factor 4E-binding protein 1; eIF2α, eukaryotic translation initiation factor 2α; eIF4E, eukaryotic translation initiation factor 4E; ER, estrogen receptor; ERK1/2, extracellular signal-related kinase 1/2; FAK, focal adhesion kinase; FAS, tumor necrosis factor receptor superfamily, member 6; FGFR, fibroblast growth factor receptor; FOXO1, forkhead box O1; GRB2, growth factor receptor-bound protein 2; HIF-1α, hypoxia inducible factor-1; HLJ-1, DNA J-like heat shock protein-1; IκB, inhibitory κB; ICAM-1, intracellular adhesion molecule-1; IGF1R, insulin-like growth factor 1 receptor; IFNα, interferon α; IL, interleukin; JAK, Janus kinase; JNK, c-Jun N-terminal activated kinase; LC3-II, microtubule-associated protein light chain 3-II; MAPK, mitogen-activated protein kinase; MEKK3, mitogen-activated protein kinase kinase kinase 3; miRNA, micro RNA; MKK7, mitogen-activated protein kinase kinase 7; MMP2/9, matrix metallopreotease 2/9; NCAM, neural cell adhesion molecule; NFκB, nuclear factor κB; PAK1, P21 protein (Cdc42/Rac)-activated kinase 1; PARP, poly ADP ribose polymerase; p-EGFR, phosphorylated epithelial growth factor receptor; PI3K, phosphatidyl inositol 3 kinase; PKC, protein kinase C; Rac-1, Ras-related C3 botulinum toxin substrate 1; Ras, rat sarcoma; RhoA, Ras homolog gene family, member A; SP-1, specificity protein-1; STAT3, signal transducer and activator of transcription 3; TGFβ1, transforming growth factor β1; TNFα, tumor necrosis factor α; TOPO-IIa, topoisomerase IIa; VEGF, vascular endothelial growth factor; WIF-1, Wnt inhibitory factor-1; XIAP, X-linked inhibitor of apoptosis.