Green tea catechin EGCG suppresses NUDT6 (nudix [nucleoside diphosphate linked moiety X]‐type motif 6) expression in human colorectal cancer

Abstract

A natural antisense RNA of FGF‐2, FGF‐ AS, has been implicated to modulate the function of pro‐angiogenic factor FGF‐2 (bFGF). FGF‐AS RNA encodes a novel nudix motif protein, NUDT6 /GFG, whose function is not yet known. The main aim of this study was to characterize the transcriptional regulation and biological function of this protein. Our microarray data showed that a green tea component, epigallocatechin (ECG), suppressed NUDT6 expression, and this was confirmed by RT‐PCR. Subsequently, the use of different catechins showed that the effect of epigallocatechin gallate (EGCG) was stronger than that of ECG. At the post‐transcriptional level, EGCG affected the RNA stability of NUDT6, indicating it as a potential mechanism of NUDT6 suppression. To further define the underlying mechanism of biological function of NUDT6 in human colorectal cancer cells, we constructed the NUDT6 correct (pool) and reverse (control) orientation clones, tagged with V5. These plasmids were transfected and selected under G418 in HCT‐116 cells to generate stable cell lines for control and NUDT6. Using these cell systems, we found that NUDT6 expression increased cell growth, soft agar cloning efficiency, and colony formation, compared to the control cells. There was also decreased 3/7‐caspase activity in pool compared to control. We conclude that NUDT6 is a novel cell proliferator in colorectal cancer and is down‐regulated by the green tea catechin EGCG.