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
Abstract

Paclitaxel (taxol) inhibits protein isoprenylation and induces apoptosis in PC-3 human prostate cancer cells.

R Danesi, W D Figg, E Reed and C E Myers
Molecular Pharmacology June 1995, 47 (6) 1106-1111;
R Danesi
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
W D Figg
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
E Reed
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
C E Myers
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Info & Metrics
  • eLetters
  • PDF
Loading

Abstract

Paclitaxel was examined for its effects on cell survival, internucleosomal DNA fragmentation, and protein isoprenylation in the human prostate cancer cell line PC-3. Treatment of cells with paclitaxel at 5-60 nM for 24 hr resulted in a dose-dependent inhibition of cell viability (IC50, 31.2 nM), which was partially prevented by supplementing the cell culture medium with two nonsterol polyisoprenyl compounds, farnesyl-pyrophosphate (-PP) and geranylgeranyl-PP (3 microM each). Furthermore, agarose gel electrophoresis of DNA extracted from cells treated with paclitaxel (15-60 nM) for 24 hr showed DNA laddering with production of fragments of 180-base pair multiples, indicating the occurrence of apoptotic cell death. Internucleosomal DNA fragmentation by paclitaxel was also detected by a photometric enzyme immunoassay using antihistone antibodies; if culture medium was supplemented with farnesyl-PP and geranylgeranyl-PP (3 microM each), a reduction in mono- and oligonucleosome production was observed. The post-translational incorporation of metabolites of (RS)-[5-3H]mevalonolactone (100 microCi/ml) into prenylated proteins of PC-3 cells was inhibited by paclitaxel at 30 and 60 nM. In addition, the immunoprecipitation of p21ras and p21rap-1 proteins from PC-3 cells exposed to paclitaxel (30 and 60 nM) and labeled with (RS)-[5-3H]mevalonolactone showed a substantial inhibition of the incorporation of farnesyl and geranylgeranyl prenoid groups, respectively, into the aforementioned proteins. These results indicate that the inhibition of protein isoprenylation is a novel component of the complex biochemical effects of the drug and plays an important role in the mechanism of paclitaxel cytotoxicity in PC-3 cells.

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
Vol. 47, Issue 6
1 Jun 1995
  • Table of Contents
  • Table of Contents (PDF)
  • 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.
Paclitaxel (taxol) inhibits protein isoprenylation and induces apoptosis in PC-3 human prostate cancer cells.
(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
Abstract

Paclitaxel (taxol) inhibits protein isoprenylation and induces apoptosis in PC-3 human prostate cancer cells.

R Danesi, W D Figg, E Reed and C E Myers
Molecular Pharmacology June 1, 1995, 47 (6) 1106-1111;

Citation Manager Formats

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

Share
Abstract

Paclitaxel (taxol) inhibits protein isoprenylation and induces apoptosis in PC-3 human prostate cancer cells.

R Danesi, W D Figg, E Reed and C E Myers
Molecular Pharmacology June 1, 1995, 47 (6) 1106-1111;
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
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

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