Inhibitory effects of gallic acid and quercetin on UDP-glucose dehydrogenase activity

Hwang, Eun Young; Huh, Jae-Wan; Choi, Myung-Min; Choi, Soo Young; Hong, Hea-Nam; Cho, Sung-Woo

doi:10.1016/j.febslet.2008.10.010

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Volume 582, Issue 27 , Pages 3793-3797, 12 November 2008

Inhibitory effects of gallic acid and quercetin on UDP-glucose dehydrogenase activity

Edited by Judit Ovádi

Eun Young Hwang
- Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul 138-736, Republic of Korea
Jae-Wan Huh
- Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul 138-736, Republic of Korea
- Corresponding authors. Fax: +82 2 3010 4278.
Myung-Min Choi
- Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul 138-736, Republic of Korea
Soo Young Choi
- Department of Biomedical Sciences and Research Institute for Bioscience and Biotechnology, Hallym University, Chunchon, Republic of Korea
Hea-Nam Hong
- Department of Anatomy and Cell Biology, University of Ulsan College of Medicine, Seoul, Republic of Korea
Sung-Woo Cho
- Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul 138-736, Republic of Korea
- Corresponding authors. Fax: +82 2 3010 4278.

Received 23 June 2008; received in revised form 26 September 2008; accepted 7 October 2008. published online 17 October 2008.

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.

Abbreviations: UGDH, UDP-glucose dehydrogenase

Keywords: UDP-glucose dehydrogenase, Gallic acid, Quercetin, Breast cancer cell