Curcumin inhibits lung cancer cell invasion and metastasis through the tumor suppressor HLJ1

Cancer Res. 2008 Sep 15;68(18):7428-38. doi: 10.1158/0008-5472.CAN-07-6734.


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 mumol/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 mumol/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 NH(2)-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Animals
  • Cadherins / biosynthesis
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Movement / physiology
  • Curcumin / pharmacology*
  • HSP40 Heat-Shock Proteins / biosynthesis*
  • HSP40 Heat-Shock Proteins / genetics
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • MAP Kinase Kinase 4 / metabolism
  • Mice
  • Mice, SCID
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Proto-Oncogene Proteins c-jun / metabolism
  • Random Allocation
  • Signal Transduction
  • Transcription Factor AP-1 / genetics
  • Transcription Factor AP-1 / metabolism
  • Transfection
  • Up-Regulation


  • Cadherins
  • DNAJB4 protein, human
  • HSP40 Heat-Shock Proteins
  • Proto-Oncogene Proteins c-jun
  • Transcription Factor AP-1
  • MAP Kinase Kinase 4
  • Curcumin