Curcumin suppresses constitutive activation of AP-1 by downregulation of JunD protein in HTLV-1-infected T-cell lines

Leuk Res. 2006 Mar;30(3):313-21. doi: 10.1016/j.leukres.2005.08.004. Epub 2005 Sep 12.


Activation of the activator protein 1 (AP-1) plays a critical role in oncogenesis by human T-cell leukemia virus type 1 (HTLV-1), the etiologic agent of adult T-cell leukemia (ATL), and is required for maintenance of the malignant phenotype. Curcumin (diferuloylmethane), the major pigment of the spice turmeric, has anti-tumor activity; however, the effect of curcumin against ATL has not been elucidated. In this study, we examined the effects of curcumin on AP-1 activity in HTLV-1-infected T-cell lines. Curcumin suppressed the constitutive AP-1 DNA-binding and transcriptional activity in HTLV-1-infected T-cell line. Curcumin also inhibited HTLV-1 Tax-induced AP-1 transcriptional activity. JunD was detectable as a major component of the AP-1-DNA complex in HTLV-1-infected T-cell lines using the supershift assay. The expression of JunD was suppressed by curcumin treatment. Curcumin inhibited the growth of HTLV-1-infected T-cell lines by inducing cell cycle arrest followed by apoptosis. Our results suggest that suppression of the constitutively active AP-1 by curcumin is due to, at least in-part, reducing the expression of JunD by curcumin. Inhibition of AP-1 activity by curcumin may be one of the mechanisms responsible for the anti-ATL effect of curcumin. We propose that curcumin is a potentially promising compound for the treatment of ATL.

Publication types

  • Research Support, Non-U.S. Gov't
  • Retracted Publication

MeSH terms

  • Apoptosis / drug effects
  • Cell Cycle / drug effects
  • Cell Line
  • Curcumin / pharmacology*
  • Curcumin / therapeutic use
  • Enzyme Inhibitors / pharmacology*
  • Enzyme Inhibitors / therapeutic use
  • Gene Expression Regulation, Leukemic / drug effects
  • Gene Expression Regulation, Viral / drug effects
  • Genes, pX / drug effects
  • Human T-lymphotropic virus 1 / metabolism*
  • Humans
  • Leukemia-Lymphoma, Adult T-Cell / drug therapy
  • Leukemia-Lymphoma, Adult T-Cell / metabolism*
  • Leukemia-Lymphoma, Adult T-Cell / pathology
  • Proto-Oncogene Proteins c-jun / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-jun / metabolism
  • T-Lymphocytes / metabolism*
  • T-Lymphocytes / pathology
  • T-Lymphocytes / virology
  • Transcription Factor AP-1 / metabolism*
  • Transcription, Genetic / drug effects


  • Enzyme Inhibitors
  • Proto-Oncogene Proteins c-jun
  • Transcription Factor AP-1
  • Curcumin