Anti-invasive gene expression profile of curcumin in lung adenocarcinoma based on a high throughput microarray analysis.
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 microM) and that this anti-invasive effect was concentration dependent (10.17 +/- 0.76 x 10(3) cells at 0 microM; 5.67 +/- 1.53 x 10(3) cells at 1 microM; 2.67 +/- 0.58 x 10(3) cells at 5 microM; 1.15 +/- 1.03 x 10(3) cells at 10 microM; 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 microM), several invasion-related genes were suppressed, including matrix metalloproteinase 14 (MMP14; 0.65-fold), neuronal cell adhesion molecule (0.54-fold), and integrins alpha6 (0.67-fold) and beta4 (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 microM) 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.
Chen
Huei-Wen
HW
Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan, ROC.
Yu
Sung-Liang
SL
Chen
Jeremy J W
JJ
Li
Han-Ni
HN
Lin
Yi-Chen
YC
Yao
Pei-Li
PL
Chou
Han-Yi
HY
Chien
Chiang-Ting
CT
Chen
Wen-Jone
WJ
Lee
Yuan-Teh
YT
Yang
Pan-Chyr
PC
D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000473:pathology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D016328:NF-kappa B / Q000502:physiology; D009361:Neoplasm Invasiveness; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D016328:NF-kappa B; D020778:Matrix Metalloproteinase 2; D003474:Curcumin