Epicatechin gallate-induced expression of NAG-1 is associated with growth inhibition and apoptosis in colon cancer cells.
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-beta 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 G(1) 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-microM 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.
Laboratory of Environmental Carcinogenesis, Department of Pathobiology, College of Veterinary Medicine, University of Tennessee, 2407 River Drive, Knoxville, TN 37996, USA. sbaek2@utk.edu
Seung Joon
SJ
Baek
Jong-Sik
JS
Kim
Felix R
FR
Jackson
Thomas E
TE
Eling
Michael F
MF
McEntee
Seong-Ho
SH
Lee
D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D016193:G1 Phase / Q000187:drug effects; D055436:Growth Differentiation Factor 15; D045325:HCT116 Cells; D006801:Humans; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D013662:Tea; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D000975:Antioxidants; D016207:Cytokines; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15; D013662:Tea; D016159:Tumor Suppressor Protein p53; D002392:Catechin; C062669:epicatechin gallate; D011065:Poly(ADP-ribose) Polymerases