Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • 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
  • 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
    • 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
  • Visit molpharm on Facebook
  • Follow molpharm on Twitter
  • Follow molpharm on LinkedIn
Research ArticleArticle

Altered Drug Interaction and Regulation of Topoisomerase IIβ: Potential Mechanisms Governing Sensitivity of HL-60 Cells to Amsacrine and Etoposide

Dale R. Grabowski, Katherine A. Holmes, Masako Aoyama, Ying Ye, Lisa A. Rybicki, Ronald M. Bukowski, Mahrukh K. Ganapathi, Ian D. Hickson and Ram Ganapathi
Molecular Pharmacology December 1999, 56 (6) 1340-1345; DOI: https://doi.org/10.1124/mol.56.6.1340
Dale R. Grabowski
Experimental Therapeutics Program, Taussig Cancer Center, Cleveland Clinic Foundation, Cleveland, Ohio; and the Molecular Oncology Laboratory, Imperial Cancer Research Fund Unit, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, United Kingdom
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Katherine A. Holmes
Experimental Therapeutics Program, Taussig Cancer Center, Cleveland Clinic Foundation, Cleveland, Ohio; and the Molecular Oncology Laboratory, Imperial Cancer Research Fund Unit, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, United Kingdom
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Masako Aoyama
Experimental Therapeutics Program, Taussig Cancer Center, Cleveland Clinic Foundation, Cleveland, Ohio; and the Molecular Oncology Laboratory, Imperial Cancer Research Fund Unit, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, United Kingdom
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ying Ye
Experimental Therapeutics Program, Taussig Cancer Center, Cleveland Clinic Foundation, Cleveland, Ohio; and the Molecular Oncology Laboratory, Imperial Cancer Research Fund Unit, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, United Kingdom
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Lisa A. Rybicki
Experimental Therapeutics Program, Taussig Cancer Center, Cleveland Clinic Foundation, Cleveland, Ohio; and the Molecular Oncology Laboratory, Imperial Cancer Research Fund Unit, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, United Kingdom
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ronald M. Bukowski
Experimental Therapeutics Program, Taussig Cancer Center, Cleveland Clinic Foundation, Cleveland, Ohio; and the Molecular Oncology Laboratory, Imperial Cancer Research Fund Unit, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, United Kingdom
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mahrukh K. Ganapathi
Experimental Therapeutics Program, Taussig Cancer Center, Cleveland Clinic Foundation, Cleveland, Ohio; and the Molecular Oncology Laboratory, Imperial Cancer Research Fund Unit, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, United Kingdom
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ian D. Hickson
Experimental Therapeutics Program, Taussig Cancer Center, Cleveland Clinic Foundation, Cleveland, Ohio; and the Molecular Oncology Laboratory, Imperial Cancer Research Fund Unit, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, United Kingdom
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ram Ganapathi
Experimental Therapeutics Program, Taussig Cancer Center, Cleveland Clinic Foundation, Cleveland, Ohio; and the Molecular Oncology Laboratory, Imperial Cancer Research Fund Unit, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, United Kingdom
  • 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

Topoisomerase II (topo II), an enzyme essential for cell viability, is present in mammalian cells as the α- and β-isoforms. In human leukemia HL-60/S or HL-60/doxorubicin (DOX)0.05 cells, the levels of topo IIα- or β-protein were similar in either asynchronous exponential or synchronized cultures. Although topo IIα was hypophosphorylated in HL-60/DOX0.05 compared with HL-60/S cells, both overall and site-specific hyperphosphorylation of topo IIβ was apparent in HL-60/DOX0.05 compared with HL-60/S cells. The phosphorylation of topo IIα and not β was enhanced in the S and G2 + M phases of HL-60/S cells. In contrast, an increase in the phosphorylation of topo IIβ compared with α was apparent in the G1 and S phases of HL-60/DOX0.05 cells. The cytotoxicity and depletion of topo IIα or β in cells treated with drug for 1 h revealed that mole-for-mole, amsacrine was 2-fold more effective than etoposide in killing HL-60/S or HL-60/DOX0.05 cells and in depleting the β versus α topo II protein. Present results demonstrate that: 1) hyperphosphorylation of topo IIβ in HL-60/DOX0.05 cells may be a compensatory consequence of the hypophosphorylation of topo IIα to maintain normal topo II function during proliferation, and 2) enhanced sensitivity of HL-60/S or HL-60/DOX0.05 cells to amsacrine may be due to the preferential interaction and depletion of topo IIβ.

Footnotes

    • Received July 12, 1999.
    • Accepted September 15, 1999.
  • Send reprint requests to: Dr. Ram Ganapathi, Taussig Cancer Center M38, Cleveland Clinic Foundation, 9500 Euclid Ave., Cleveland, OH 44195. E-mail: ganapar{at}cc.ccf.org

  • This work was supported by U.S. Public Health Service Grant CA35531 and Grant CA74939 from the Department of Health and Human Services (to K.A.H., D.R.G., M.A., Y.Y., M.K.G., and R.G.), and by the Imperial Cancer Research Fund (I.D.H.).

  • 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: 56 (6)
Molecular Pharmacology
Vol. 56, Issue 6
1 Dec 1999
  • 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.
Altered Drug Interaction and Regulation of Topoisomerase IIβ: Potential Mechanisms Governing Sensitivity of HL-60 Cells to Amsacrine and Etoposide
(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

Altered Drug Interaction and Regulation of Topoisomerase IIβ: Potential Mechanisms Governing Sensitivity of HL-60 Cells to Amsacrine and Etoposide

Dale R. Grabowski, Katherine A. Holmes, Masako Aoyama, Ying Ye, Lisa A. Rybicki, Ronald M. Bukowski, Mahrukh K. Ganapathi, Ian D. Hickson and Ram Ganapathi
Molecular Pharmacology December 1, 1999, 56 (6) 1340-1345; DOI: https://doi.org/10.1124/mol.56.6.1340

Citation Manager Formats

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

Altered Drug Interaction and Regulation of Topoisomerase IIβ: Potential Mechanisms Governing Sensitivity of HL-60 Cells to Amsacrine and Etoposide

Dale R. Grabowski, Katherine A. Holmes, Masako Aoyama, Ying Ye, Lisa A. Rybicki, Ronald M. Bukowski, Mahrukh K. Ganapathi, Ian D. Hickson and Ram Ganapathi
Molecular Pharmacology December 1, 1999, 56 (6) 1340-1345; DOI: https://doi.org/10.1124/mol.56.6.1340
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
    • Abstract
    • Materials and Methods
    • Results
    • Discussion
    • Acknowledgments
    • Footnotes
    • Abbreviations
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • 6-Methylflavone Blocks Bitterness of Tenofovir
  • Positive Allosteric Modulation of the mGlu5 Receptor
  • Correction of mutant CNGA3 channel trafficking defect
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 © 2021 by the American Society for Pharmacology and Experimental Therapeutics