Xenograft Studies of Fatty Acid Synthesis Inhibition as Novel Therapy for Breast Cancer
Abstract
This grant proposed to study the effect of fatty acid synthesis inhibition in human breast cancer xenografts using C75, a novel inhibitor of fatty acid synthesis. We also proposed to study the mechanism of cell death by C75 and the effect of dietary fatty acids on this model. The purpose of this study is to demonstrate that the fatty acid synthesis is a novel pathway for breast cancer therapy development. We found that C75 inhibited fatty acid synthase (FAS) and had significant anti-tumor activity in both human breast cancer and human mesothelioma xenografts. In addition, we determined that malonyl-CoA is likely the trigger of apoptosis during FAS inhibition in cancer cells. During treatment of animals with C75, we noted significant reversible weight loss. Mechanistic studies of the weight loss showed that FAS inhibition leads to reduced neuropeptide-Y production in the hypothalamus. Thus, we have found that inhibition of FAS in mammals has a significant anti-tumor effect. In addition, FAS inhibition can cause weight reduction and correction of Type II diabetes in obese (ob/ob) mice.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2000
- Accession Number
- ADB268439
Entities
People
- Francis P. Kuhajda
Organizations
- Johns Hopkins University