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

Differential Roles of p21Waf1 and p27Kip1in Modulating Chemosensitivity and Their Possible Application in Drug Discovery Studies

Mathias Schmidt, Yang Lu, John M. Parant, Guillermina Lozano, Gerald Bacher, Thomas Beckers and Zhen Fan
Molecular Pharmacology November 2001, 60 (5) 900-906; DOI: https://doi.org/10.1124/mol.60.5.900
Mathias Schmidt
Departments of 1 2 3
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yang Lu
Departments of 1 2 3
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
John M. Parant
Departments of 1 2 3
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Guillermina Lozano
Departments of 1 2 3
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Gerald Bacher
Departments of 1 2 3
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Thomas Beckers
Departments of 1 2 3
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Zhen Fan
Departments of 1 2 3
  • 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 this study, the differential role of the cyclin-dependent kinase (CDK) inhibitors p21Waf1 and p27Kip1 in cell cycle regulation was proposed for use in screening natural or synthetic compounds for cell cycle-dependent (particularly M phase-dependent) antineoplastic activity. p21Waf1 or p27Kip1 was ectopically expressed with an ecdysone-inducible mammalian expression system in a human colon adenocarcinoma cell line. Induction of p21Waf1 or p27Kip1 expression inhibited the activities of CDK2 and completely arrested cells at G1phase of the cell cycle by p27Kip1 and at G1and G2 phases by p21Waf1. We examined the sensitivity of these cells to several antineoplastic agents known to be cell cycle-dependent or -independent. Substantially increased resistance to cell cycle-dependent antineoplastic agents was found in the cells when the expression of p21Waf1 or p27Kip1 was induced. In contrast, only a desensitization to cell cycle-independent antineoplastic agents was found in the cells arrested by p21Waf1 or p27Kip1. Because p21Waf1 induces an additional block at G2 phase that inhibits cell entry into M phase, we further examined the difference between p21Waf1- and p27Kip1-induced cells in their sensitivity to D-24851, a novel M phase-dependent compound. We found that induction of p21Waf1 after exposure of the cells to D-24851 conferred stronger resistance than did induction of p27Kip1. Taken together, our results suggest that the differential effect of p21Waf1 and p27Kip1 on cell cycle regulation may be advantageous for screening chemical libraries for novel antineoplastic candidates that are cell cycle-dependent, and M phase-dependent in particular.

  • 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: 60 (5)
Molecular Pharmacology
Vol. 60, Issue 5
1 Nov 2001
  • 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 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.
Differential Roles of p21Waf1 and p27Kip1in Modulating Chemosensitivity and Their Possible Application in Drug Discovery Studies
(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

Differential Roles of p21Waf1 and p27Kip1in Modulating Chemosensitivity and Their Possible Application in Drug Discovery Studies

Mathias Schmidt, Yang Lu, John M. Parant, Guillermina Lozano, Gerald Bacher, Thomas Beckers and Zhen Fan
Molecular Pharmacology November 1, 2001, 60 (5) 900-906; DOI: https://doi.org/10.1124/mol.60.5.900

Citation Manager Formats

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

Share
Research ArticleArticle

Differential Roles of p21Waf1 and p27Kip1in Modulating Chemosensitivity and Their Possible Application in Drug Discovery Studies

Mathias Schmidt, Yang Lu, John M. Parant, Guillermina Lozano, Gerald Bacher, Thomas Beckers and Zhen Fan
Molecular Pharmacology November 1, 2001, 60 (5) 900-906; DOI: https://doi.org/10.1124/mol.60.5.900
Reddit logo Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Experimental Procedures
    • Results
    • Discussion
    • Acknowledgments
    • Footnotes
    • Abbreviations
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Antimicrobial and Antileukemic Transportan 10 Conjugates
  • Pharmacological characterization of zebrafish H1 receptor
  • Bhave and Forman
Show more Article

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