Development of Novel Anti-prostate cancer drugs based on modification of Sphingolipid Metabolism
Dr S Gatt, The Hebrew University of Jerusalem , Israel

Ceremide, the precursor of all sphingolipids as well as the product of their hydrolysis, is involved in signalling that leads to apoptotic cell death of a variety of cancer cells, including those of prostate cancer. Thus, elevation of ceramide in prostate cancer cells by metabolic intervention increased their sensitivity to radiation as well as chemotherapeutic agents. We have synthesized novel, non-natural sphingolipid analogs that were cytotoxic to cancer cells and were shown to inhibit the biosynthesis of sphongomyelin and glucosylceramide as well as the hydrolysis of acid ceramidase, resulting in an elevation of cellular ceramide and induction of apoptotic cell death.

Dr Gatt and the team at the Hebrew University

We propose to extend these syntheses aiming at compounds that will increase the levels of ceramide in prostate cancer cells, androgen sensitive and insensitive, resulting in their sensitisation to chemotherapy and radiation. The synthetic analogues will be predominantly tested on prostate cancer cells grown in culture, by themselves and in combination with suitable chemotherapeutic drugs. Our ultimate aim is to locate sphingolipid analogues that would serve as novel drugs for therapy of prostate cancer, by themselves with cytotoxic agents that are currently in clinical use.

Project commenced
November 2004

Length of project
1 year

Amount Supported
£44,000