Curcumin causes the growth arrest and apoptosis of B cell lymphoma by downregulation of egr-1, c-myc, bcl-XL, NF-kappa B, and p53

Clin Immunol. 1999 Nov;93(2):152-61. doi: 10.1006/clim.1999.4769.

Abstract

It has been well known that curcumin is a powerful inhibitor of proliferation of several tumor cells. However, the molecular basis of the anti-proliferative effect of curcumin has not been investigated in detail. In this paper, we present evidence to show that curcumin inhibited proliferation of a variety of B lymphoma cells. At low concentrations curcumin inhibited the proliferation of BKS-2, an immature B cell lymphoma, more effectively than that of normal B lymphocytes and caused the apoptosis of BKS-2 cells in a dose- and time-dependent manner. Furthermore, curcumin downregulated the expression of survival genes egr-1, c-myc, and bcl-X(L) as well as the tumor suppressor gene p53 in B cells. In addition, NF-kappaB binding activity was also downregulated almost completely by curcumin. Stimulation with CpG oligonucleotides or anti-CD40 overcame growth inhibition induced by low concentrations of curcumin. Our results suggest that curcumin caused the growth arrest and apoptosis of BKS-2 immature B cell lymphoma by downregulation of growth and survival promoting genes.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Curcumin / pharmacology*
  • DNA-Binding Proteins / antagonists & inhibitors
  • DNA-Binding Proteins / biosynthesis
  • Dose-Response Relationship, Drug
  • Down-Regulation* / drug effects
  • Early Growth Response Protein 1
  • Growth Inhibitors / antagonists & inhibitors
  • Growth Inhibitors / pharmacology*
  • Immediate-Early Proteins*
  • Lymphoma, B-Cell / drug therapy
  • Lymphoma, B-Cell / metabolism*
  • Lymphoma, B-Cell / pathology*
  • Mice
  • Mice, Inbred CBA
  • Mice, Inbred DBA
  • Mice, SCID
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / biosynthesis
  • Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis
  • Proto-Oncogene Proteins c-myc / antagonists & inhibitors
  • Proto-Oncogene Proteins c-myc / biosynthesis
  • Signal Transduction / drug effects
  • Transcription Factors / antagonists & inhibitors
  • Transcription Factors / biosynthesis*
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / antagonists & inhibitors
  • Tumor Suppressor Protein p53 / biosynthesis
  • bcl-X Protein

Substances

  • Bcl2l1 protein, mouse
  • DNA-Binding Proteins
  • Early Growth Response Protein 1
  • Egr1 protein, mouse
  • Growth Inhibitors
  • Immediate-Early Proteins
  • NF-kappa B
  • Proto-Oncogene Proteins c-bcl-2
  • Proto-Oncogene Proteins c-myc
  • Transcription Factors
  • Tumor Suppressor Protein p53
  • bcl-X Protein
  • Curcumin