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Carcinogenesis Advance Access published online on August 12, 2004
Carcinogenesis, doi:10.1093/carcin/bgh255
© 2004 by Oxford University Press
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Received April 27, 2004
Revised July 27, 2004
Accepted August 2, 2004

MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION

Epicatechin gallate-induced expression of NAG-1 is associated with growth inhibition and apoptosis in colon cancer cells

Seung Joon Baek 1*, Jong-Sik Kim 2, Felix R. Jackson 1, Thomas E. Eling 2, Michael F. McEntee 1, Seong-Ho Lee 1

1 Laboratory of Environmental Carcinogenesis, Department of Pathobiology, College of Veterinary Medicine, University of Tennessee, 2407 River Drive, Knoxville, TN 37996
2 Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709

* To whom correspondence should be addressed. E-mail: sbaek2{at}utk.edu.


  Abstract

There is persuasive epidemiological and experimental evidence that dietary polyphenolic plant-derived compounds have anti-cancer activity. Many laboratories, including ours, have reported such an effect in cancers of the gastrointestinal tract, lung, skin, prostate, and breast. The catechins are a group of polyphenols found in green tea, which is one of the most commonly consumed beverages in the world. While the preponderance of the data strongly indicates significant anti-tumorigenic benefits from the green tea catechins, the potential molecular mechanisms involved remain obscure. We found that green tea components induce apoptosis via a TGF-{beta} superfamily protein, NAG-1 (Nonsteroidal anti-inflammatory drug Activated Gene). In this report, we show that ECG is the strongest NAG-1 inducer among the tested catechins and that treatment of HCT-116 cells results in an increasing G1 sub-population, and cleavage of poly (ADP-ribose) polymerase (PARP), consistent with apoptosis. In contrast, other catechins do not significantly induce NAG-1 expression, PARP cleavage or morphological changes at up to 50 µM concentration. Furthermore, we provide evidence that ECG induces the ATF3 transcription factor, followed by NAG-1 induction at the transcriptional level in a p53 independent manner. The data generated by this study will help elucidate mechanisms of action for components in green tea and this information may lead to the design of more effective anti-cancer agents and informed clinical trials.

Keywords: NAG-1; catechins; apoptosis; ATF3; colon cancer.
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