A potential proliferative gene, NUDT6, is down-regulated by green tea catechins at the posttranscriptional level.
The main aims of this study were to elucidate the effect of green tea catechins on Nudix-type motif 6 (NUDT6) suppression and to characterize NUDT6's biological activity. Our microarray data showed that the green tea component epicatechin-3-gallate suppressed NUDT6 expression, and this was confirmed by RT-PCR. Subsequently, the use of different catechins showed that the effect of epigallocatechin-3-gallate (EGCG) was stronger than that of other catechins. At the posttranscriptional level, EGCG decreased the RNA stability of NUDT6, indicating it as a potential mechanism of NUDT6 suppression. Further cloning of the 3' untranslated region of human NUDT6 mRNA resulted in reduced luciferase activity by EGCG treatment. This effect was at least, in part, mediated by the extracellular-signal-regulated kinase and p38MAPK pathways. Finally, increased cell proliferation and cell growth in soft agar were observed in NUDT6-overexpressing cells. These findings provide a novel mechanism for the suppression of the proliferative gene NUDT6 by green tea catechins in human colorectal cancer.
Sukhthankar
Mugdha
M
Laboratory of Environmental Carcinogenesis, Department of Pathobiology, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996, USA.
Choi
Chang K
CK
English
Anthony
A
Kim
Jong-Sik
JS
Baek
Seung Joon
SJ
D020413:3' Untranslated Regions / Q000187:drug effects; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D015179:Colorectal Neoplasms / Q000517:prevention & control; D015536:Down-Regulation / Q000187:drug effects*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors; D006207:Half-Life; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D011506:Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020871:RNA Stability / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013662:Tea / Q000737:chemistry*; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors
D020413:3' Untranslated Regions; D016588:Anticarcinogenic Agents; C548962:NUDT6 protein, human; D011506:Proteins; D012333:RNA, Messenger; D013662:Tea; D002392:Catechin; C062669:epicatechin gallate; C045651:epigallocatechin gallate; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases