Inhibition of fatty acid synthesis induces programmed cell death in human breast cancer cells

One of the key limiting factors in the treatment of advanced stage human epithelial malignancies is the lack of new, selective molecular targets for antineoplastic therapy. A substantial subset of human breast, ovarian, endometrial, colorectal, and prostatic cancers express elevated levels of fatty...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1996-06, Vol.56 (12), p.2745-2747
Main Authors: PIZER, E. S, JACKISCH, C, WOOD, F. D, PASTERNACK, G. R, DAVIDSON, N. E, KUHAJDA, F. P
Format: Article
Language:English
Subjects:
Antifungal Agents - pharmacology
Antineoplastic agents
Apoptosis
Biological and medical sciences
Breast Neoplasms - metabolism
Breast Neoplasms - pathology
Cerulenin - pharmacology
DNA, Neoplasm - analysis
Fatty Acid Synthases - antagonists & inhibitors
Fatty Acids - biosynthesis
Female
General aspects
Humans
Medical sciences
Pharmacology. Drug treatments
Tumor Cells, Cultured
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Summary:One of the key limiting factors in the treatment of advanced stage human epithelial malignancies is the lack of new, selective molecular targets for antineoplastic therapy. A substantial subset of human breast, ovarian, endometrial, colorectal, and prostatic cancers express elevated levels of fatty acid synthase, the major enzyme required for endogenous fatty acid biosynthesis, and carcinoma lines are growth inhibited by cerulenin, a noncompetitive inhibitor of fatty acid synthase. We have shown previously that the difference in fatty acid biosynthesis between cancer and normal cells is an exploitable target for metabolic inhibitors in the in vitro setting and in vivo in a human ovarian carcinoma xenograft in nude mice. Here, we report that cerulenin treatment of human breast cancer cells inhibits fatty acid synthesis within 6 h after exposure, that loss of clonogenic capacity occurs within the same interval, and that DNA fragmentation and morphological changes characteristic of apoptosis ensue.
ISSN:0008-5472
1538-7445