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

Ellen S. Pizer, Christian Jackisch, Fawn D. Wood, Gary R. Pasternack, Nancy E. Davidson, Francis P. Kuhajda

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2745-2747
Number of pages3
JournalCancer Research
Volume56
Issue number12
StatePublished - Jun 15 1996

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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