Journal Article

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

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

in Carcinogenesis

Volume 25, issue 12, pages 2425-2432
Published in print December 2004 | ISSN: 0143-3334
Published online December 2004 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgh255
Epicatechin gallate-induced expression of NAG-1 is associated with growth inhibition and apoptosis in colon cancer cells

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There is persuasive epidemiological and experimental evidence that dietary polyphenolic plant-derived compounds have anticancer 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 antitumorigenic benefits from the green tea catechins, the potential molecular mechanisms involved remain obscure. We found that green tea components induce apoptosis via a TGF-β superfamily protein, NAG-1 (Non-steroidal 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 a 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 anticancer agents and informed clinical trials.

Keywords: ATF3, activating transcription factor 3; EC, (−)-epicatechin; ECG, (−)-epicatechin gallate; EGC, (−)-epigallocatechin; EGCG, (−)-epigallocatechin gallate; NAG-1, NSAID-activated gene-1; NSAIDs, non-steroidal anti-inflammatory drugs; PARP, poly(ADP-ribose) polymerase; TSP1, thrombospondin-1

Journal Article.  6376 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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