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.
Skip Nav Destination
Article navigation
April 2003
- PDF Icon PDF LinkFront Matter
Review Article|
April 15 2003
Killing tumours by ceramide-induced apoptosis: a critique of available drugs
Norman S. RADIN
Norman S. RADIN
1
Mental Health Research Institute, University of Michigan, Ann Arbor, MI, U.S.A.
1Address for correspondence: 10150 Torre Ave.–Apt. 115, Cupertino, CA 95014, U.S.A. (e-mail gluconorm@aol.com).
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
December 04 2002
Revision Received:
January 22 2003
Accepted:
January 31 2003
Accepted Manuscript online:
January 31 2003
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2003
2003
Biochem J (2003) 371 (2): 243–256.
Article history
Received:
December 04 2002
Revision Received:
January 22 2003
Accepted:
January 31 2003
Accepted Manuscript online:
January 31 2003
Citation
Norman S. RADIN; Killing tumours by ceramide-induced apoptosis: a critique of available drugs. Biochem J 15 April 2003; 371 (2): 243–256. doi: https://doi.org/10.1042/bj20021878
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Captcha Validation Error. Please try again.