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
Molecular Pharmacology
  • 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
Molecular Pharmacology

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 molpharm on Facebook
  • Follow molpharm on Twitter
  • Follow molpharm on LinkedIn
Research ArticleArticle

Amurensin G, a Potent Natural SIRT1 Inhibitor, Rescues Doxorubicin Responsiveness via Down-Regulation of Multidrug Resistance 1

Won Keun Oh, Kyoung Bin Cho, Tran Thi Hien, Tae Hyung Kim, Hyung Sik Kim, Trong Tuan Dao, Hyo-Kyung Han, Seong-Min Kwon, Sang-Gun Ahn, Jung-Hoon Yoon, Tae Hyun Kim, Yoon Gyoon Kim and Keon Wook Kang
Molecular Pharmacology November 2010, 78 (5) 855-864; DOI: https://doi.org/10.1124/mol.110.065961
Won Keun Oh
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kyoung Bin Cho
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tran Thi Hien
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tae Hyung Kim
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hyung Sik Kim
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Trong Tuan Dao
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hyo-Kyung Han
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Seong-Min Kwon
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sang-Gun Ahn
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jung-Hoon Yoon
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tae Hyun Kim
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yoon Gyoon Kim
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Keon Wook Kang
  • 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 + SI
  • PDF
Loading

Abstract

The transition from a chemotherapy-responsive cancer to a chemotherapy-resistant one is accompanied by increased expression of multidrug resistance 1 (MDR1, p-glycoprotein), which plays an important role in the efflux from the target cell of many anticancer agents. We recently showed that a Forkhead box-containing protein of the O subfamily 1 (FoxO1) is a key regulator of MDR1 gene transcription. Because nuclear localization of FoxO1 is regulated by silent information regulator two ortholog 1 (SIRT1) deacetylase, we wondered whether SIRT1 dominates MDR1 gene expression in breast cancer cells. Overexpression of SIRT1 enhanced both FoxO reporter activity and nuclear levels of FoxO1. Protein expression of MDR1 and gene transcriptional activity were also up-regulated by SIRT1 overexpression. In addition, SIRT1 inhibition reduced both nuclear FoxO1 levels and MDR1 expression in doxorubicin-resistant breast cancer cells (MCF-7/ADR) cells. A potent SIRT1 inhibitor, amurensin G (from Vitis amurensis), was identified by screening plant extracts and bioassay-guided fractionation. The compound suppressed FoxO1 activity and MDR1 expression in MCF-7/ADR cells. Moreover, pretreatment of MCF-7/ADR cells with 1 μg/ml amurensin G for 24 h increased cellular uptake of doxorubicin and restored the responsiveness of MCF-7/ADR cells to doxorubicin. In xenograft studies, injection of 10 mg/kg i.p. amurensin G substantially restored the ability of doxorubicin to inhibit MCF-7/ADR-induced tumor growth. These results suggest that SIRT1 is a potential therapeutic target of MDR1-mediated chemoresistance and that it may be possible to develop amurensin G as a useful agent for chemoresistance reversal.

Footnotes

  • ↵Embedded Image The online version of this article (available at http://molpharm.aspetjournals.org) contains supplemental material.

  • This work was supported by the National Research Foundation of Korea, funded by the Korean government [Grants 2009-0083757, 2010-0001707, R13-2008-010-01001-0].

  • Article, publication date, and citation information can be found at http://molpharm.aspetjournals.org.

    doi:10.1124/mol.110.065961.

  • ABBREVIATIONS:

    MDR
    multidrug resistance
    ABC
    ATP-binding cassette
    MRP
    multidrug resistance-associated protein
    FoxO
    Forkhead box-containing protein, O subfamily
    SIRT1
    silent information regulator two ortholog 1
    siRNA
    small-interfering RNA
    FBS
    fetal bovine serum
    PMSF
    phenylmethylsulfonyl fluoride
    PBS
    phosphate-buffered saline
    MS
    mass spectrometry
    MTT
    3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide
    PCNA
    proliferating cell nuclear antigen
    PI3
    phosphatidylinositol 3
    FHRE
    forkhead-response element
    R-123
    Rhodamine-123
    MCF-7/ADR
    doxorubicin-resistant breast cancer cells
    TUNEL
    terminal deoxynucleotidyl transferase dUTP nick-end labeling.

  • Received April 29, 2010.
  • Accepted August 16, 2010.
  • Copyright © 2010 The American Society for Pharmacology and Experimental Therapeutics
View Full Text

MolPharm 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

Molecular Pharmacology: 78 (5)
Molecular Pharmacology
Vol. 78, Issue 5
1 Nov 2010
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Back Matter (PDF)
  • Editorial Board (PDF)
  • Front Matter (PDF)
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Molecular Pharmacology 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.
Amurensin G, a Potent Natural SIRT1 Inhibitor, Rescues Doxorubicin Responsiveness via Down-Regulation of Multidrug Resistance 1
(Your Name) has forwarded a page to you from Molecular Pharmacology
(Your Name) thought you would be interested in this article in Molecular Pharmacology.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleArticle

Amurensin G, a Potent Natural SIRT1 Inhibitor, Rescues Doxorubicin Responsiveness via Down-Regulation of Multidrug Resistance 1

Won Keun Oh, Kyoung Bin Cho, Tran Thi Hien, Tae Hyung Kim, Hyung Sik Kim, Trong Tuan Dao, Hyo-Kyung Han, Seong-Min Kwon, Sang-Gun Ahn, Jung-Hoon Yoon, Tae Hyun Kim, Yoon Gyoon Kim and Keon Wook Kang
Molecular Pharmacology November 1, 2010, 78 (5) 855-864; DOI: https://doi.org/10.1124/mol.110.065961

Citation Manager Formats

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

Share
Research ArticleArticle

Amurensin G, a Potent Natural SIRT1 Inhibitor, Rescues Doxorubicin Responsiveness via Down-Regulation of Multidrug Resistance 1

Won Keun Oh, Kyoung Bin Cho, Tran Thi Hien, Tae Hyung Kim, Hyung Sik Kim, Trong Tuan Dao, Hyo-Kyung Han, Seong-Min Kwon, Sang-Gun Ahn, Jung-Hoon Yoon, Tae Hyun Kim, Yoon Gyoon Kim and Keon Wook Kang
Molecular Pharmacology November 1, 2010, 78 (5) 855-864; DOI: https://doi.org/10.1124/mol.110.065961
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
    • Introduction
    • Materials and Methods
    • Results
    • Discussion
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF + SI
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • The binding site for KCI807 in the androgen receptor
  • Fatty acid amide hydrolase in cisplatin nephrotoxicity
  • eCB Signaling System in hiPSC-Derived Neuronal Cultures
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 Molecular Pharmacology
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Drug Metabolism and Disposition
  • Journal of Pharmacology and Experimental Therapeutics
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0111 (Online)

Copyright © 2023 by the American Society for Pharmacology and Experimental Therapeutics