Curcumin and Colon Cancer
Curcumin inhibits human colon cancer cell growth by suppressing gene
expression of epidermal growth factor receptor through reducing the activity
of the transcription factor Egr-1
Alternative Medicine Review, Dec, 2005
by A. Chen, J. Xu, AC. Johnson
High expression of epidermal growth factor receptor (EGFR) is found in a variety of solid tumors,
including colorectal cancer. EGFR has been identified as a rational target for anticancer therapy.
Curcumin, the yellow pigment of turmeric in curry, has received attention as a promising dietary
supplement for cancer prevention and treatment.
We recently reported that curcumin inhibited the growth of human colon cancer-derived Moser cells
by suppressing gene expression of cyclinD1 and EGFR. The aim of the present study was to
explore the molecular mechanisms underlying curcumin inhibition of gene expression of EGFR in
colon cancer cells. The generality of the inhibitory effect of curcumin on gene expression of EGFR
was verified in other human colon cancer-derived cell lines, including Caco-2 and HT-29 cells.
Promoter deletion assays and site-directed mutageneses identified a binding site for the
transcription factor early growth response-1 (Egr-1) in egfr promoter as a putative curcumin
response element in regulating the promoter activity of the gene in Moser cells. Electrophoretic
mobility shift assays demonstrated that curcumin significantly reduced the DNA-binding activity of
the transcription factor Egr-1 to the curcumin response element. In addition, curcumin reduced the
trans-activation activity of Egr-1 by suppressing egr-1 gene expression, which required interruption
of the ERK signal pathway and reduction of the level of phosphorylation of Elk- 1 and its activity.
Taken together, our results demonstrated that curcumin inhibited human colon cancer cell growth by
suppressing gene expression of EGFR through reducing the trans-activation activity of Egr-1. These
results provided novel insights into the mechanisms of curcumin inhibition of colon cancer cell
growth and potential therapeutic strategies for treatment of colon cancer.
expression of epidermal growth factor receptor through reducing the activity
of the transcription factor Egr-1
Alternative Medicine Review, Dec, 2005
by A. Chen, J. Xu, AC. Johnson
High expression of epidermal growth factor receptor (EGFR) is found in a variety of solid tumors,
including colorectal cancer. EGFR has been identified as a rational target for anticancer therapy.
Curcumin, the yellow pigment of turmeric in curry, has received attention as a promising dietary
supplement for cancer prevention and treatment.
We recently reported that curcumin inhibited the growth of human colon cancer-derived Moser cells
by suppressing gene expression of cyclinD1 and EGFR. The aim of the present study was to
explore the molecular mechanisms underlying curcumin inhibition of gene expression of EGFR in
colon cancer cells. The generality of the inhibitory effect of curcumin on gene expression of EGFR
was verified in other human colon cancer-derived cell lines, including Caco-2 and HT-29 cells.
Promoter deletion assays and site-directed mutageneses identified a binding site for the
transcription factor early growth response-1 (Egr-1) in egfr promoter as a putative curcumin
response element in regulating the promoter activity of the gene in Moser cells. Electrophoretic
mobility shift assays demonstrated that curcumin significantly reduced the DNA-binding activity of
the transcription factor Egr-1 to the curcumin response element. In addition, curcumin reduced the
trans-activation activity of Egr-1 by suppressing egr-1 gene expression, which required interruption
of the ERK signal pathway and reduction of the level of phosphorylation of Elk- 1 and its activity.
Taken together, our results demonstrated that curcumin inhibited human colon cancer cell growth by
suppressing gene expression of EGFR through reducing the trans-activation activity of Egr-1. These
results provided novel insights into the mechanisms of curcumin inhibition of colon cancer cell
growth and potential therapeutic strategies for treatment of colon cancer.
| Clear up your Colon with Curcumin |