https://scholars.lib.ntu.edu.tw/handle/123456789/502922
標題: | Curcumin inhibits lung cancer cell invasion and metastasis through the tumor suppressor HLJ1 | 作者: | HUEI-WEN CHEN Lee J.-Y. Huang J.-Y. Wang C.-C. Chen W.-J. SHENG-FANG SU Huang C.-W. CHAO-CHI HO Chen J.J.W. Tsai M.-F. SUNG-LIANG YU PAN-CHYR YANG |
公開日期: | 2008 | 卷: | 68 | 期: | 18 | 起(迄)頁: | 7428-7438 | 來源出版物: | Cancer Research | 摘要: | 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 upregulates 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. ?2008 American Association for Cancer Research. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/502922 | ISSN: | 0008-5472 | DOI: | 10.1158/0008-5472.CAN-07-6734 | SDG/關鍵字: | anthra[1,9 cd]pyrazol 6(2h) one; curcumin; heat shock protein 40; luciferase; propylene glycol; protein DnaJ; protein hlj1; small interfering RNA; stress activated protein kinase; transcription factor AP 1; transcription factor JunD; tumor suppressor protein; unclassified drug; uvomorulin; animal experiment; animal model; antineoplastic activity; article; binding site; cancer cell; cancer invasion; cell migration; concentration response; controlled study; enhancer region; enzyme phosphorylation; flow cytometry; human; human cell; immunofluorescence; lung adenocarcinoma; metastasis; mouse; nonhuman; priority journal; promoter region; protein expression; reverse transcription polymerase chain reaction; transcription regulation; treatment duration; Western blotting; Adenocarcinoma; Animals; Cadherins; Cell Line, Tumor; Cell Movement; Curcumin; HSP40 Heat-Shock Proteins; Humans; Lung Neoplasms; MAP Kinase Kinase 4; Mice; Mice, SCID; Neoplasm Invasiveness; Neoplasm Metastasis; Proto-Oncogene Proteins c-jun; Random Allocation; Signal Transduction; Transcription Factor AP-1; Transfection; Up-Regulation |
顯示於: | 醫學檢驗暨生物技術學系 |
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