Accession Number : ADA478482


Title :   Fatty Acid Synthase Inhibitors Engage the Cell Death Program Through the Endoplasmic Reticulum


Descriptive Note : Annual rept. 1 Dec 2006-30 Nov 2007


Corporate Author : WAKE FOREST UNIV WINSTON-SALEM NC SCHOOL OF HEALTH SCIENCES


Personal Author(s) : Kridel, Steven J


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a478482.pdf


Report Date : Dec 2007


Pagination or Media Count : 106


Abstract : Fatty acid synthase (FAS), the enzyme that synthesizes the 16-carbon fatty acid palmitate, in highly expressed in prostate cancer. Because of a corresponding lack of expression in normal prostate, FAS is an attractive drug target. We have described the endoplasmic reticulum (ER) stress response as a critical mediator of the anti-tumor effects of FAS inhibitors. In this report we also describe a novel connection between the FAS pathway and the proteasome pathway. This feedback between the two pathways can further be antagonized by co-treatment with the FDA-approved proteasome inhibitor Velcade. Velcade synergizes with FAS inhibitors to induce cell death and increase ER stress related signaling. These aspects will be followed up in vitro and in vivo. The importance of these studies is underscored by the potential relevance of FAS as a drug target in prostate cancer. Several FAS inhibitors have been developed, but none have been translated into the clinic thus far. These studies will be valuable as FAS inhibitors move toward a clinical setting.


Descriptors :   *SYNTHASES , *ENZYME INHIBITORS , *PROSTATE CANCER , CELLS(BIOLOGY) , APOPTOSIS


Subject Categories : Genetic Engineering and Molecular Biology
      Medicine and Medical Research
      Pharmacology


Distribution Statement : APPROVED FOR PUBLIC RELEASE