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

FEBS Lett. 2008 Nov 12;582(27):3793-7. doi: 10.1016/j.febslet.2008.10.010. Epub 2008 Oct 16.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / enzymology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Enzyme Inhibitors / pharmacology*
  • Gallic Acid / pharmacology*
  • Humans
  • NAD / pharmacology
  • Quercetin / pharmacology*
  • Uridine Diphosphate Glucose / pharmacology
  • Uridine Diphosphate Glucose Dehydrogenase / antagonists & inhibitors*

Substances

  • Enzyme Inhibitors
  • NAD
  • Gallic Acid
  • Quercetin
  • Uridine Diphosphate Glucose Dehydrogenase
  • Uridine Diphosphate Glucose