A potential proliferative gene, NUDT6, is down-regulated by green tea catechins at the posttranscriptional level

Sukhthankar, Mugdha; Choi, Chang K.; English, Anthony; Kim, Jong-Sik; Baek, Seung Joon

doi:10.1016/j.jnutbio.2008.11.002

« Previous Next »The Journal of Nutritional Biochemistry
Volume 21, Issue 2 , Pages 98-106, February 2010

A potential proliferative gene, NUDT6, is down-regulated by green tea catechins at the posttranscriptional level

Mugdha Sukhthankar
- Laboratory of Environmental Carcinogenesis, Department of Pathobiology, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996, USA
Chang K. Choi
- Laboratory of Environmental Carcinogenesis, Department of Pathobiology, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996, USA
Anthony English
- Department of Mechanical, Aerospace and Biomedical Engineering, College of Engineering, University of Tennessee, Knoxville, TN 37996, USA
Jong-Sik Kim
- Department of Biology, Andong National University, Andong 760-749, South Korea
Seung Joon Baek
- Laboratory of Environmental Carcinogenesis, Department of Pathobiology, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996, USA
- Corresponding author. Tel.: +1 865 974 8216; fax: +1 865 974 5616.

Received 8 July 2008; received in revised form 23 October 2008; accepted 11 November 2008. published online 21 January 2009.

Abstract

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.

Abbreviations: UTR, untranslated region, ARE, AU-rich element, DMSO, dimethyl sulfoxide, EGCG, epigallocatechin-3-gallate, EGC, epigallocatechin, ECG, epicatechin-3-gallate, EC, epicatechin, ERK, extracellular-signal-regulated kinase, FGF-2, fibroblast growth factor-2, NUDT6, Nudix-type motif 6