|Title:||Anti-Invasive Gene Expression Profile of Curcumin in Lung Adenocarcinoma Based on a High Throughput Microarray Analysis||Authors:||HUEI-WEN CHEN
HAN-YI E. CHOU
|Issue Date:||2004||Journal Volume:||65||Journal Issue:||1||Start page/Pages:||99-110||Source:||Molecular Pharmacology||Abstract:||
Curcumin has been reported to exhibit anti-invasive and/or antimetastatic activities, but the mechanism remains unclear. In this study, microarray analysis of gene expression profiles were used to characterize the anti-invasive mechanisms of curcumin in highly invasive lung adenocarcinoma cells (CL1-5). Results showed that curcumin significantly reduces the invasive capacity of CL1-5 cells in a concentration range far below its levels of cytotoxicity (20 μM) and that this anti-invasive effect was concentration dependent (10.17 ± 0.76 × 103 cells at 0 μM; 5.67 ± 1.53 × 103 cells at 1 μM; 2.67 ± 0.58 × 103 cells at 5 μM; 1.15 ± 1.03 × 10 3 cells at 10 μM; P < 0.05) in the Transwell cell culture chamber assay. Using microarray analysis, 81 genes were down-regulated and 71 genes were up-regulated after curcumin treatment. Below sublethal concentrations of curcumin (10 μM), several invasion-related genes were suppressed, including matrix metalloproteinase 14 (MMP14; 0.65-fold), neuronal cell adhesion molecule (0.54-fold), and integrins α6 (0.67-fold) and β4 (0.63-fold). In addition, several heat-shock proteins (Hsp) [Hsp27 (2.78-fold), Hsp70 (3.75-fold), and Hsp40-like protein (3.21-fold)] were induced by curcumin. Real-time quantitative reverse transcription-polymerase chain reaction, Western blotting, and immunohistochemistry confirmed these results in both RNA and protein levels. Curcumin (1 to 10 μM) reduced the MMP14 expression in both mRNA and protein levels and also inhibited the activity of MMP2, the down-stream gelatinase of MMP14, by gelatin zymographic analysis. Based on these data, it can be concluded that curcumin might be an effective antimetastatic agent with a mechanism of anti-invasion via the regulation of certain gene expressions.
|URI:||https://scholars.lib.ntu.edu.tw/handle/123456789/466273||ISSN:||0026-895X||DOI:||10.1124/mol.65.1.99||SDG/Keyword:||alpha6 integrin; beta4 integrin; curcumin; gelatinase A; gelatinase B; heat shock protein 27; heat shock protein 40; heat shock protein 70; immunoglobulin enhancer binding protein; matrigel; matrix metalloproteinase 14; messenger RNA; nerve cell adhesion molecule; apoptosis; article; cancer invasion; cell viability; controlled study; DNA microarray; drug cytotoxicity; drug mechanism; enzyme activity; gene expression regulation; high throughput screening; human; human cell; immunohistochemistry; lung adenocarcinoma; metastasis inhibition; nucleotide sequence; priority journal; quantitative analysis; real time polymerase chain reaction; transcription regulation; unindexed sequence; Western blotting; zymography; Antineoplastic Agents; Blotting, Western; Cell Survival; Curcumin; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Lung Neoplasms; Matrix Metalloproteinase 2; Neoplasm Invasiveness; NF-kappa B; Oligonucleotide Array Sequence Analysis; Reverse Transcriptase Polymerase Chain Reaction; Transcription, Genetic; Tumor Cells, Cultured
|Appears in Collections:||醫學院附設醫院 (臺大醫院)|
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