Skip to main content

Main menu

  • Home
  • About the Journal
    • General Information
    • Scope
    • Editorial Board
    • Impact & Metrics
    • Benefits of Publishing
    • Advertising/Sponsorship
    • About the Biochemical Society
  • Current Issue
  • For Authors
    • Submit Your Paper
    • Submission Guidelines
    • Editorial Policy
    • Open Access Policy
    • Rights and Permissions
    • Biochemical Society Member Benefits
  • For Librarians
    • Subscriptions and Pricing
    • Check Your Usage
    • Terms and Conditions
      • Biochemical Journal- Terms and Conditions of Usage
    • Open Access Policy
    • FAQs for Librarians
    • Register for Free Trial
  • For Readers
    • Subscribe
    • Rights and Permissions
    • Biochemical Society Member Benefits
    • Journal Access for Biochemical Society Members
    • Request a Free Trial
  • Collections
    • Article Collections
    • Classic Articles
  • Help
    • Technical Support
    • Contact Us
  • Other Publications
    • Biochemical Journal
    • Clinical Science
    • Bioscience Reports
    • Neuronal Signaling
    • Biochemical Society Transactions
    • Essays in Biochemistry
    • Emerging Topics in Life Sciences
    • Biochemical Society Symposia
    • Cell Signalling Biology
    • Glossary of Biochemistry and Molecular Biology
    • The Biochemist
    • Biochemical Society

User menu

  • Log-in
  • Subscribe
  • Contact Us

Search

  • Advanced search
  • Other Publications
    • Biochemical Journal
    • Clinical Science
    • Bioscience Reports
    • Neuronal Signaling
    • Biochemical Society Transactions
    • Essays in Biochemistry
    • Emerging Topics in Life Sciences
    • Biochemical Society Symposia
    • Cell Signalling Biology
    • Glossary of Biochemistry and Molecular Biology
    • The Biochemist
    • Biochemical Society

Log-in

Sign-up for alerts  
  • My Cart
Biochemical Journal
Browse Archive
Advanced Search
  • Home
  • About the Journal
    • General Information
    • Scope
    • Editorial Board
    • Impact & Metrics
    • Benefits of Publishing
    • Advertising/Sponsorship
    • About the Biochemical Society
  • Current Issue
  • For Authors
    • Submit Your Paper
    • Submission Guidelines
    • Editorial Policy
    • Open Access Policy
    • Rights and Permissions
    • Biochemical Society Member Benefits
  • For Librarians
    • Subscriptions and Pricing
    • Check Your Usage
    • Terms and Conditions
    • Open Access Policy
    • FAQs for Librarians
    • Register for Free Trial
  • For Readers
    • Subscribe
    • Rights and Permissions
    • Biochemical Society Member Benefits
    • Journal Access for Biochemical Society Members
    • Request a Free Trial
  • Collections
    • Article Collections
    • Classic Articles
  • Help
    • Technical Support
    • Contact Us

Review article

Killing tumours by ceramide-induced apoptosis: a critique of available drugs

Norman S. RADIN
Biochemical Journal Apr 15, 2003, 371 (2) 243-256; DOI: 10.1042/bj20021878
Norman S. RADIN
Mental Health Research Institute, University of Michigan, Ann Arbor, MI, U.S.A.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • View author's works on this site
  • Article
  • Info & Metrics
  • PDF
Loading

Abstract

Over 1000 research papers have described the production of programmed cell death (apoptosis) by interventions that elevate the cell content of ceramide (Cer). Other interventions, which lower cellular Cer, have been found to interfere with apoptosis induced by other agents. Some studies have shown that slowing the formation of proliferation-stimulating sphingolipids also induces apoptosis. These relationships are due to the two different aspects of Cer: Cer itself produces apoptosis, but metabolic conversion of Cer into either sphingosine 1-phosphate or glucosphingolipids leads to cell proliferation. The balance between these two aspects is missing in cancer cells, and yet intervention by stimulating or blocking only one or two of the pathways in Cer metabolism is very likely to fail. This results from two properties of cancer cells: their high mutation rate and the preferential survival of the most malignant cells. Tumours treated with only one or two drugs that elevate Cer can adjust the uncontrolled processes to either maintain or to ‘aggravate’ the excessive growth, angiogenesis and metastasis characteristics of tumours. These treatments might simply elevate the production of growth factors, receptors and other substances that reduce the effectiveness of Cer. Tumour cells that do not adapt in this way undergo apoptosis, leaving the adapted cells free to grow and, ultimately, to ‘subdue’ their host. Thus it is important to kill every type of cancer cell present in the tumour rapidly and simultaneously, using as many different agents to control as many pathways as possible. To aid this approach, this article catalogues many of the drugs that act on different aspects of Cer metabolism. The techniques described here may lead to the development of practical chemotherapy for cancer and other diseases of excess proliferation.

  • glutathione depletion
  • glucosphingolipid-induced proliferation
  • multidrug resistance
  • poly-drug chemotherapy
  • reactive oxygen species
  • sphingolipid

Footnotes

  • Abbreviations used: Cer, ceramide; C2-Cer, N-acetylsphingosine; COX-2, cyclo-oxygenase-2; CPZ, chlorpromazine; DAG, diacylglycerol; GlcCer, glucosylceramide; GSL, glucosphingolipid; LDL, low-density lipoprotein; d-MAPP, d-erythro-2-tetradecanoylamino-1-phenyl-1-propanol; MDR, multidrug resistance; NSAIDs, non-steroidal anti-inflammatory drugs; P4 (or PPPP), d-threo-1-phenyl-2-palmitoylamino-3-pyrrolidino-1-propanol; PDMP, d-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol; PPMP, d,l-threo-(1-phenyl-2-hexadecanoylamino-3-morpholino-1-propanol); PtdCho, phosphatidylcholine; PtdSer, phosphatidylserine; ROS, reactive oxygen species; S1P, sphingosine 1-phosphate; SM(ase), sphingomyelin(ase); SPT, serine palmitoyltransferase; THC, tetrahydrocannabinol; UDP-Glc, UDP-glucose.

  • The Biochemical Society, London ©2003
Previous ArticleNext Article
Back to top

 

April 2003

Volume: 371 Issue: 2

  • Table of Contents
  • Index by author
  • Front Matter (PDF)

Actions

Email

Thank you for your interest in spreading the word about Biochemical Journal.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Killing tumours by ceramide-induced apoptosis: a critique of available drugs
(Your Name) has forwarded a page to you from Biochemical Journal
(Your Name) thought you would like to see this page from the Biochemical Journal web site.
Share
Killing tumours by ceramide-induced apoptosis: a critique of available drugs
Norman S. RADIN
Biochemical Journal Apr 2003, 371 (2) 243-256; DOI: 10.1042/bj20021878
del.icio.us logo Digg logo Reddit logo Technorati logo Twitter logo CiteULike logo Facebook logo Mendeley logo
Citation Tools
Killing tumours by ceramide-induced apoptosis: a critique of available drugs
Norman S. RADIN
Biochemical Journal Apr 2003, 371 (2) 243-256; DOI: 10.1042/bj20021878

Citation Manager Formats

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

Please log in to add an alert for this article.

Request Permissions
Save to my folders

View Full PDF

 Open in Utopia Docs
  • Tweet Widget
  • Facebook Like

Jump To

  • Article
  • Info & Metrics
  • PDF

Keywords

glutathione depletion
glucosphingolipid-induced proliferation
multidrug resistance
poly-drug chemotherapy
reactive oxygen species
sphingolipid

Related Articles

Cited By...

  • Portland Press Homepage
  • Publish With Us
  • Advertising
  • Technical Support
  • Biochemical Journal
  • Clinical Science
  • Essays in Biochemistry
  • Emerging Topics in Life Sciences
  • Biochemical Society Transactions
  • Neuronal Signaling
  • Bioscience Reports
  • Cell Signalling Biology
  • Biochemical Society Symposia

Portland Press Limited
Charles Darwin House
12 Roger Street
London WC1N 2JU
Email: editorial@portlandpress.com

The Biochemical Society