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.
Copyright 1999 Academic Press.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Apoptosis / drug effects*
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Curcumin / pharmacology*
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DNA-Binding Proteins / antagonists & inhibitors
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DNA-Binding Proteins / biosynthesis
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Dose-Response Relationship, Drug
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Down-Regulation* / drug effects
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Early Growth Response Protein 1
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Growth Inhibitors / antagonists & inhibitors
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Growth Inhibitors / pharmacology*
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Immediate-Early Proteins*
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Lymphoma, B-Cell / drug therapy
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Lymphoma, B-Cell / metabolism*
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Lymphoma, B-Cell / pathology*
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Mice
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Mice, Inbred CBA
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Mice, Inbred DBA
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Mice, SCID
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NF-kappa B / antagonists & inhibitors
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NF-kappa B / biosynthesis
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Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors
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Proto-Oncogene Proteins c-bcl-2 / biosynthesis
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Proto-Oncogene Proteins c-myc / antagonists & inhibitors
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Proto-Oncogene Proteins c-myc / biosynthesis
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Signal Transduction / drug effects
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Transcription Factors / antagonists & inhibitors
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Transcription Factors / biosynthesis*
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Tumor Cells, Cultured
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Tumor Suppressor Protein p53 / antagonists & inhibitors
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Tumor Suppressor Protein p53 / biosynthesis
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bcl-X Protein
Substances
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Bcl2l1 protein, mouse
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DNA-Binding Proteins
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Early Growth Response Protein 1
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Egr1 protein, mouse
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Growth Inhibitors
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Immediate-Early Proteins
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NF-kappa B
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Proto-Oncogene Proteins c-bcl-2
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Proto-Oncogene Proteins c-myc
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Transcription Factors
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Tumor Suppressor Protein p53
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bcl-X Protein
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Curcumin