Skip to main content
  • AACR Publications
    • Blood Cancer Discovery
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

AACR logo

  • Register
  • Log in
  • Log out
  • My Cart
Advertisement

Main menu

  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Meeting Abstracts
    • Collections
      • COVID-19 & Cancer Resource Center
      • Focus on Computer Resources
      • Highly Cited Collection
      • Editors' Picks
      • "Best of" Collection
  • For Authors
    • Information for Authors
    • Author Services
    • Early Career Award
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • Editors' Picks
    • OnlineFirst
    • Citations
    • Author/Keyword
    • RSS Feeds
    • My Alert Summary & Preferences
  • News
    • Cancer Discovery News
  • COVID-19
  • Webinars
  • Search More

    Advanced Search

  • AACR Publications
    • Blood Cancer Discovery
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

User menu

  • Register
  • Log in
  • Log out
  • My Cart

Search

  • Advanced search
Cancer Research
Cancer Research
  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Meeting Abstracts
    • Collections
      • COVID-19 & Cancer Resource Center
      • Focus on Computer Resources
      • Highly Cited Collection
      • Editors' Picks
      • "Best of" Collection
  • For Authors
    • Information for Authors
    • Author Services
    • Early Career Award
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • Editors' Picks
    • OnlineFirst
    • Citations
    • Author/Keyword
    • RSS Feeds
    • My Alert Summary & Preferences
  • News
    • Cancer Discovery News
  • COVID-19
  • Webinars
  • Search More

    Advanced Search

Epidemiology and Prevention

Characterization of Vincristine Transport by the Mr 190,000 Multidrug Resistance Protein (MRP): Evidence for Cotransport with Reduced Glutathione

Douglas W. Loe, Roger G. Deeley and Susan P. C. Cole
Douglas W. Loe
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Roger G. Deeley
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Susan P. C. Cole
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
DOI:  Published November 1998
  • Article
  • Info & Metrics
  • PDF
Loading

Abstract

The Mr 190,000 multidrug resistance protein (MRP) confers resistance to a broad spectrum of natural product drugs. However, it has not been possible to demonstrate that MRP can actively transport unmodified forms of these compounds, although the protein has been shown to transport structurally diverse glutathione (GSH)- and glucuronide-conjugated molecules. Previously, we showed that ATP-dependent uptake of vincristine by MRP-enriched, inside-out membrane vesicles could be stimulated by physiological concentrations of GSH (Loe et al., J. Biol. Chem., 271: 9675–9682, 1996). We have now established that the ATP/GSH dependent vincristine uptake is both proportional to the level of MRP in the membrane vesicles and can be inhibited by monoclonal antibodies shown previously to inhibit transport of established MRP substrates, such as leukotriene C4. We also show that short-chain alkyl derivatives of GSH can stimulate drug uptake, which suggests that vincristine transport does not necessarily involve a change in redox state or glutathionylation of the protein. Furthermore, vincristine uptake is accompanied by ATP- and drug-dependent accumulation of GSH, which can also be stimulated to a lesser extent by vinblastine but not daunorubicin or doxorubicin. Although GSH or vincristine alone are very poor inhibitors of MRP-mediated transport of leukotriene C4, together they act as relatively potent competitive inhibitors. Overall, our data demonstrate that MRP can actively cotransport GSH and unmodified vincristine and that these compounds probably interact, either with the leukotriene C4 binding site(s) on the protein or with a mutually exclusive site.

Footnotes

  • ↵1 Supported by Grant MT-10519 from the Medical Research Council of Canada. R. G. D. is the Stauffer Research Professor of Queen's University, and S. P. C. C. is a Senior Scientist of Cancer Care Ontario.

  • ↵2 To whom requests for reprints should be addressed, at Cancer Research Laboratories, Room 328, Botterell Hall, Queen's University, Kingston, Ontario, Canada, K7L 3N6. Phone: (613) 545-6507; Fax: (613) 545-6830; E-mail: coles@post.queensu.ca.

  • Received March 24, 1998.
  • Accepted September 16, 1998.
  • ©1998 American Association for Cancer Research.
PreviousNext
Back to top
November 1998
Volume 58, Issue 22
  • Table of Contents
  • Table of Contents (PDF)
  • Back Matter (PDF)
  • Editorial Board (PDF)
  • Front Matter (PDF)

Sign up for alerts

Open full page PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Cancer Research 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.
Characterization of Vincristine Transport by the Mr 190,000 Multidrug Resistance Protein (MRP): Evidence for Cotransport with Reduced Glutathione
(Your Name) has forwarded a page to you from Cancer Research
(Your Name) thought you would be interested in this article in Cancer Research.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Characterization of Vincristine Transport by the Mr 190,000 Multidrug Resistance Protein (MRP): Evidence for Cotransport with Reduced Glutathione
Douglas W. Loe, Roger G. Deeley and Susan P. C. Cole
Cancer Res November 15 1998 (58) (22) 5130-5136;

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Characterization of Vincristine Transport by the Mr 190,000 Multidrug Resistance Protein (MRP): Evidence for Cotransport with Reduced Glutathione
Douglas W. Loe, Roger G. Deeley and Susan P. C. Cole
Cancer Res November 15 1998 (58) (22) 5130-5136;
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
  • Info & Metrics
  • PDF
Advertisement

Related Articles

Cited By...

More in this TOC Section

Epidemiology and Prevention

  • Inhibition of Prostate Cancer Growth by Muscadine Grape Skin Extract and Resveratrol through Distinct Mechanisms
  • Seizure 6-Like (SEZ6L) Gene and Risk for Lung Cancer
  • Strong Evidence of a Genetic Determinant for Mammographic Density, a Major Risk Factor for Breast Cancer
Show more Epidemiology and Prevention

Articles

  • Laureate Citations
  • Role of TCL1 and ALL1 in Human Leukemias and Development
  • The Partial Homeodomain of the Transcription Factor Pax-5 (BSAP) Is an Interaction Motif for the Retinoblastoma and TATA-binding Proteins
Show more Articles
  • Home
  • Alerts
  • Feedback
  • Privacy Policy
Facebook  Twitter  LinkedIn  YouTube  RSS

Articles

  • Online First
  • Current Issue
  • Past Issues
  • Meeting Abstracts

Info for

  • Authors
  • Subscribers
  • Advertisers
  • Librarians

About Cancer Research

  • About the Journal
  • Editorial Board
  • Permissions
  • Submit a Manuscript
AACR logo

Copyright © 2021 by the American Association for Cancer Research.

Cancer Research Online ISSN: 1538-7445
Cancer Research Print ISSN: 0008-5472
Journal of Cancer Research ISSN: 0099-7013
American Journal of Cancer ISSN: 0099-7374

Advertisement