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Inhibitory effects of gallic acid and quercetin on UDP-glucose dehydrogenase activity
Authors:Hwang Eun Young  Huh Jae-Wan  Choi Myung-Min  Choi Soo Young  Hong Hea-Nam  Cho Sung-Woo
Institution:a Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul 138-736, Republic of Korea
b Department of Biomedical Sciences and Research Institute for Bioscience and Biotechnology, Hallym University, Chunchon, Republic of Korea
c Department of Anatomy and Cell Biology, University of Ulsan College of Medicine, Seoul, Republic of Korea
Abstract:We have examined polyphenols as potential inhibitors of UDP-glucose dehydrogenase (UGDH) activity. Gallic acid and quercetin decreased specific activities of UGDH and inhibited the proliferation of MCF-7 human breast cancer cells. Western blot analysis showed that gallic acid and quercetin did not affect UGDH protein expression, suggesting that UGDH activity is inhibited by polyphenols at the post-translational level. Kinetics studies using human UGDH revealed that gallic acid was a non-competitive inhibitor with respect to UDP-glucose and NAD+. In contrast, quercetin showed a competitive inhibition and a mixed-type inhibition with respect to UDP-glucose and NAD+, respectively. These results indicate that gallic acid and quercetin are effective inhibitors of UGDH that exert strong antiproliferative activity in breast cancer cells.
Keywords:UGDH  UDP-glucose dehydrogenase
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