Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Drug Metabolism & Disposition
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
  • My Cart
Drug Metabolism & Disposition

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Visit dmd on Facebook
  • Follow dmd on Twitter
  • Follow ASPET on LinkedIn
Research ArticleArticle

STRONG INHIBITORY EFFECTS OF COMMON TEA CATECHINS AND BIOFLAVONOIDS ON THE O-METHYLATION OF CATECHOL ESTROGENS CATALYZED BY HUMAN LIVER CYTOSOLIC CATECHOL-O-METHYLTRANSFERASE

Mime Nagai, Allan H. Conney and Bao Ting Zhu
Drug Metabolism and Disposition May 2004, 32 (5) 497-504; DOI: https://doi.org/10.1124/dmd.32.5.497
Mime Nagai
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Allan H. Conney
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Bao Ting Zhu
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF
Loading

Abstract

In the present investigation, we studied the inhibitory effects of three tea catechins [catechin, epicatechin, and (-)-epigallocatechin-3-O-gallate] and two bioflavonoids (quercetin and fisetin) on the O-methylation of 2- and 4-hydroxyestradiol (2-OH-E2 and 4-OH-E2, respectively) by human liver cytosolic catechol-O-methyltransferase (COMT). We found that catechin and epicatechin each inhibited the O-methylation of 2-OH-E2 and 4-OH-E2 in a concentration-dependent manner. The IC50 values for inhibition of 2-OH-E2 methylation by catechin and epicatechin were 14 to 17 μM and 44 to 65 μM, respectively, and their IC50 values for inhibition of 4-OH-E2 methylation were 5 to 7 μM and 10 to 18 μM, respectively. Our data showed that these two catechins had 2- to 6-fold higher inhibition potency for the O-methylation of 4-OH-E2 than for the O-methylation of 2-OH-E2. (-)-Epigallocatechin-3-O-gallate was found to have a distinctly high inhibition potency for the O-methylation of 2- and 4-OH-E2 (IC50 values of 0.04–0.07 μM and 0.2–0.5 μM, respectively). The crude extracts from green tea and black tea also showed very strong activity in inhibiting human liver COMT-mediated O-methylation of catechol estrogens. We also determined, for comparison, two common bioflavonoids (quercetin and fisetin) for their inhibitory effects on human liver COMT-mediated O-methylation of catechol estrogens. The IC50 values for quercetin and fisetin were 0.9 to 1.5 μM and 3.3 to 4.5 μM, respectively, for inhibiting the O-methylation of 2-OH-E2, and 0.5 to 1.2 μM and 2.6 to 4.2 μM, respectively, for inhibiting the O-methylation of 4-OH-E2. Enzyme kinetic analyses showed that both tea catechins and bioflavonoids inhibited human liver COMT-mediated O-methylation of 4-OH-E2 (a representative substrate) with a mixed mechanism of inhibition (competitive plus noncompetitive). In summary, the catechol-containing tea catechins and bioflavonoids are strong inhibitors of human liver COMT-mediated O-methylation of catechol estrogens. More studies are warranted to determine the extent of such inhibition in human subjects and the potential biological consequences.

Footnotes

  • ↵1 Abbreviations used are: 2-OH-E2, 2-hydroxyestradiol; 4-OH-E2, 4-hydroxyestradiol; COMT, catechol-O-methyltransferase; SAM, S-adenosyl-l-methionine; EGCG, (-)-epigallocatechin-3-O-gallate; BTP, black tea polyphenol(s); GTP, green tea polyphenol(s); SAH, S-adenosyl-l-homocysteine.

  • Supported in part by grants from the National Institutes of Health (RO1 CA 97109), the American Parkinson Disease Association, and the California Table Grape Commission.

    • Received November 24, 2003.
    • Accepted January 29, 2004.
  • The American Society for Pharmacology and Experimental Therapeutics
View Full Text

 

DMD articles become freely available 12 months after publication, and remain freely available for 5 years. 

Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page. 

 

  • Click here for information on institutional subscriptions.
  • Click here for information on individual ASPET membership.

 

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top

In this issue

Drug Metabolism and Disposition: 32 (5)
Drug Metabolism and Disposition
Vol. 32, Issue 5
1 May 2004
  • Table of Contents
  • About the Cover
  • Index by author
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Drug Metabolism & Disposition article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
STRONG INHIBITORY EFFECTS OF COMMON TEA CATECHINS AND BIOFLAVONOIDS ON THE O-METHYLATION OF CATECHOL ESTROGENS CATALYZED BY HUMAN LIVER CYTOSOLIC CATECHOL-O-METHYLTRANSFERASE
(Your Name) has forwarded a page to you from Drug Metabolism & Disposition
(Your Name) thought you would be interested in this article in Drug Metabolism & Disposition.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleArticle

STRONG INHIBITORY EFFECTS OF COMMON TEA CATECHINS AND BIOFLAVONOIDS ON THE O-METHYLATION OF CATECHOL ESTROGENS CATALYZED BY HUMAN LIVER CYTOSOLIC CATECHOL-O-METHYLTRANSFERASE

Mime Nagai, Allan H. Conney and Bao Ting Zhu
Drug Metabolism and Disposition May 1, 2004, 32 (5) 497-504; DOI: https://doi.org/10.1124/dmd.32.5.497

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
Research ArticleArticle

STRONG INHIBITORY EFFECTS OF COMMON TEA CATECHINS AND BIOFLAVONOIDS ON THE O-METHYLATION OF CATECHOL ESTROGENS CATALYZED BY HUMAN LIVER CYTOSOLIC CATECHOL-O-METHYLTRANSFERASE

Mime Nagai, Allan H. Conney and Bao Ting Zhu
Drug Metabolism and Disposition May 1, 2004, 32 (5) 497-504; DOI: https://doi.org/10.1124/dmd.32.5.497
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Materials and Methods
    • Results
    • Discussion
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Improved CYP Reaction Phenotyping
  • Multiple-Concentration Chemical Inhibition Design
  • New Dog P450 3A98 in Gut
Show more Articles

Similar Articles

Advertisement
  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Fast Forward by date
  • Fast Forward by section
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About DMD
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Journal of Pharmacology and Experimental Therapeutics
  • Molecular Pharmacology
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-009X (Online)

Copyright © 2022 by the American Society for Pharmacology and Experimental Therapeutics