請用此 Handle URI 來引用此文件: http://hdl.handle.net/11455/40320
標題: Curcumin inhibits lung cancer cell invasion and metastasis through the tumor suppressor HLJ1
作者: Chen, H.W.
陳健尉
Lee, J.Y.
Huang, J.Y.
Wang, C.C.
Chen, W.J.
Su, S.F.
Huang, C.W.
Ho, C.C.
Chen, J.J.W.
Tsai, M.F.
Yu, S.L.
Yang, P.C.
關鍵字: heat-shock proteins
gene-expression
chemopreventive agent
activator
protein-1
microarray analysis
breast-cancer
chaperones
proliferation
angiogenesis
complexes
期刊/報告no:: Cancer Research, Volume 68, Issue 18, Page(s) 7428-7438.
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 mu mol/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 mu mol/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.
URI: http://hdl.handle.net/11455/40320
ISSN: 0008-5472
文章連結: http://dx.doi.org/10.1158/0008-5472.can-07-6734
顯示於類別:生物醫學研究所

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