Involvement of nucleophosmin/B23 in the cellular response to curcumin

J Nutr Biochem. 2011 Jan;22(1):46-52. doi: 10.1016/j.jnutbio.2009.11.010. Epub 2010 Mar 20.

Abstract

Nucleophosmin (NPM/B23) is a nucleolar phosphoprotein involved in cellular response to many different stimuli. Herein, we studied the molecular mechanism of NPM/B23 induction by curcumin, a natural AP-1 inhibitor with antitumor properties. Exposure to 5-30 μM curcumin significantly and dose-dependently increased the level of NPM/B23 in non-transformed NIH 3T3 cells but not HeLa cells and F9 cells. Besides, the transformed F9 and HeLa cells are more sensitive to curcumin-induced cell death and growth inhibition than NIH 3T3 cells. Overexpression of c-Jun, but not c-Fos, decreased ∼40% of NPM/B23 and enhanced the sensitivity of NIH 3T3 cells to 30 μM curcumin. Furthermore, down-regulation of NPM/B23 by transfection with NPM/B23 antisense plasmid enhanced the sensitivity to curcumin-induced cell death and growth inhibition. These results indicated that NPM/B23 expression regulates cellular sensitivity to curcumin. Besides, NPM/B23 knockdown may facilitate as a novel strategy to promote the sensitivity of cancer cells to curcumin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticarcinogenic Agents / pharmacology
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Cell Line, Transformed
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Curcumin / pharmacology*
  • Embryonal Carcinoma Stem Cells
  • HeLa Cells
  • Humans
  • Mice
  • NIH 3T3 Cells
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism*
  • Neoplasms / prevention & control
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Nucleophosmin
  • Oligonucleotides, Antisense / genetics
  • Oligonucleotides, Antisense / metabolism
  • Osmolar Concentration
  • Proto-Oncogene Proteins c-jun / antagonists & inhibitors
  • Proto-Oncogene Proteins c-jun / genetics
  • Proto-Oncogene Proteins c-jun / metabolism
  • Signal Transduction / drug effects
  • Transcription Factor AP-1 / antagonists & inhibitors*
  • Transcription Factor AP-1 / genetics
  • Transcription Factor AP-1 / metabolism
  • Up-Regulation / drug effects*

Substances

  • Anticarcinogenic Agents
  • Antineoplastic Agents, Phytogenic
  • NPM1 protein, human
  • Npm1 protein, mouse
  • Nuclear Proteins
  • Oligonucleotides, Antisense
  • Proto-Oncogene Proteins c-jun
  • Transcription Factor AP-1
  • Nucleophosmin
  • Curcumin