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Obesity drug inhibits prostate tumor growth

(La Jolla, California) The Burnham Institute's Jeffrey Smith, Ph.D. has discovered that orlistat, commonly prescribed as an anti-obesity drug, has a positive side-effect: it inhibits cancer growth. Dr. Smith made this discovery using an activity-based proteomics screening technique developed in his laboratory that makes it possible to identify active targets and simultaneously screen for their inhibitors. These results will be published in the journal Cancer Research on March 15.

The metabolism of a tumor cell is different from its normal counterpart cell. Scientists have long suspected that metabolism is connected to tumor progression. Dr. Smith and co-workers designed a proteomics screen based on monitoring the activity of a family of enzymes--serine hydrolyases--involved in metabolism. They used their screen to compare normal prostate cells with prostate cancer cells and discovered that the prostate cancer cells are affected by an increased activity of fatty acid synthase. Fatty acid synthase is the enzyme that converts dietary carbohydrate to fat.

The screen also identified orlistat, marketed by Roche as XenicalTM, as an inhibitor of fatty acid synthase.

These discoveries, made in vitro, held true when tested in mice. When they administered orlistat to mice bearing prostate tumors, the Smith laboratory discovered that the drug was able to inhibit tumor growth in mice. Further experiments confirmed that orlistat has no effect on normal prostate cells and no apparent side effects in the mice; it acts specifically as fatty acid synthase.

Additional screening of breast cancer and colon cancer cells revealed that fatty acid synthase activity is upregulated in these tumors, as well, presenting the possibility of designing new treatments for these cancers based on inhibiting the enzyme's activity with orlistat or a new drug based on orlistat's inhibitory activity.

Orlistat was originally developed
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Contact: Nancy Beddingfield
nbeddingfield@burnham.org
858-646-3146
Burnham Institute
15-Mar-2004


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