Curcumin Inhibits Lung Cancer Cell Invasion and Metastasis through the Tumor Suppressor HLJ1
| Autor: | Wan-Jiun Chen, Chi-Chung Wang, Jeremy J.W. Chen, Jen-Yi Lee, Pan-Chyr Yang, Huei-Wen Chen, Meng-Feng Tsai, Ji-Ying Huang, Sung-Liang Yu, Chia-Wen Huang, Sheng-Fang Su, Chao-Chi Ho |
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| Rok vydání: | 2008 |
| Předmět: |
Cancer Research
Curcumin Lung Neoplasms Tumor suppressor gene MAP Kinase Kinase 4 Proto-Oncogene Proteins c-jun Angiogenesis Mice SCID Adenocarcinoma Biology Transfection Metastasis Mice Random Allocation chemistry.chemical_compound Cell Movement Cell Line Tumor medicine Animals Humans Neoplasm Invasiveness Neoplasm Metastasis Gene knockdown HSP40 Heat-Shock Proteins Cadherins medicine.disease Up-Regulation Transcription Factor AP-1 Oncology chemistry Cell culture Cancer cell Cancer research Signal transduction Signal Transduction |
| Zdroj: | Cancer Research. 68:7428-7438 |
| ISSN: | 1538-7445 0008-5472 |
| Popis: | Curcumin (diferuloylmethane) is an active component of the spice turmeric and has a diversity of antitumor activities. In this study, we found that curcumin can inhibit cancer cell invasion and metastasis through activation of the tumor suppressor DnaJ-like heat shock protein 40 (HLJ1). Human lung adenocarcinoma cells (CL1-5) treated with curcumin (1–20 μmol/L) showed a concentration-dependent reduction in cell migration, invasion, and metastatic ability, and this was associated with increased HLJ1 expression. Knockdown of HLJ1 expression by siRNA was able to reverse the curcumin-induced anti-invasive and antimetastasis effects in vitro and in vivo. The HLJ1 promoter and enhancer in a luciferase reporter assay revealed that curcumin transcriptionally up-regulates HLJ1 expression through an activator protein (AP-1) site within the HLJ1 enhancer. JunD, one of the AP-1 components, was significantly up-regulated by curcumin (1–20 μmol/L) in a concentration- and time-dependent manner. Knockdown of JunD expression could partially reduce the curcumin-induced HLJ1 activation and diminish the anti-invasive effect of curcumin, indicating that JunD would seem to be involved in curcumin-induced HLJ1 expression. Curcumin was able to induce c-Jun NH2-kinase (JNK) phosphorylation, whereas the JNK inhibitor (SP-600125) could attenuate curcumin-induced JunD and HLJ1 expression. Activation of HLJ1 by curcumin further leads to up-regulation of E-cadherin and a suppression of cancer cell invasion. Our results show that curcumin induces HLJ1, through activation of the JNK/JunD pathway, and inhibits lung cancer cell invasion and metastasis by modulating E-cadherin expression. This is a novel mechanism and supports the application of curcumin in anti–cancer metastasis therapy. [Cancer Res 2008;68(18):7428–38] |
| Databáze: | OpenAIRE |
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