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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

Oncogene volume 25, pages 278–287 (2006)Cite this article

Abstract

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.

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Abbreviations

EGFR:

epidermal growth factor receptor

Egr-1:

early growth response-1

EMSA:

electrophoretic mobility shift assay

ERK:

extracellular signal-regulated kinase

FBS:

fetal bovine serum

PPARγ:

peroxisome proliferator-activated receptor-gamma

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Acknowledgements

The work was supported by the grants to A Chen, from Feist-Weiller Cancer Center, LSUHSC-S, DK 47995 from NIH/NIDDK and starting funds from Department of Pathology, LSUHSC-S.

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Authors and Affiliations

  1. Department of Pathology, Louisiana State University Health Sciences Center in Shreveport, Shreveport, LA, USA

    A Chen & J Xu

  2. Department of Cellular Biology & Anatomy, Louisiana State University Health Sciences Center in Shreveport, Shreveport, LA, USA

    A Chen

  3. Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, USA

    A C Johnson

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  1. A Chen
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Correspondence to A Chen.

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Chen, A., Xu, J. & Johnson, A. 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. Oncogene 25, 278–287 (2006). https://doi.org/10.1038/sj.onc.1209019

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