Selective inhibition of fatty acid synthase for lung cancer treatment. (1/23)

PURPOSE: Fatty acid synthase (FAS) is overexpressed in many human cancers and is considered to be a promising target for therapy. However, in vitro use of previous generations of FAS inhibitors has been limited by severe, but reversible, anorexia in treated animals, which is thought to be related to a parallel stimulation of fatty acid oxidation by these agents. This study investigated pharmacologic inhibition of FAS using C93, a rationally designed molecule that inhibits FAS activity without affecting fatty acid oxidation in preclinical models of lung cancer. EXPERIMENTAL DESIGN: Activity of C93 on FAS and fatty acid oxidation was evaluated in cultured non-small cell lung cancer (NSCLC) cells. Antineoplastic activity of the compound, given orally or by i.p. injection, was evaluated in s.c. and orthotopic NSCLC xenografts. RESULTS: Our experiments confirm that C93 effectively inhibits FAS without stimulating fatty acid oxidation in lung cancer cells. More importantly, C93 significantly inhibits the growth of both s.c. and orthotopic xenograft tumors from human NSCLC cell lines without causing anorexia and weight loss in the treated animals. CONCLUSIONS: We conclude that inhibition of FAS can be achieved without parallel stimulation of fatty acid oxidation and that inhibition of tumor growth in vivo can be achieved without anorexia and weight loss. Thus, this therapeutic strategy holds promise for clinical treatment of cancers, including non-small cell lung cancer, the leading cause of cancer mortality in the United States and Europe.  (+info)

Dietary soy protein inhibits DNA damage and cell survival of colon epithelial cells through attenuated expression of fatty acid synthase. (2/23)

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Comparative anticancer effects of flavonoids and diazepam in cultured cancer cells. (3/23)

This study examined the comparative anticancer effects of flavonoids and diazepam in the cultured cancer cells. In the SNU-C4 colorectal and MDA-MB-231 breast adenocarcinoma cells, apigenin and fisetin, flavonoids, and diazepam inhibited cancer cell survival concentration and incubation-time dependently. Diazepam consistently inhibited FAS activity, a known anticancer mechanism of flavonoids, in a concentration dependent manner. Unlike diazepam, in highly aggressive breast MDA-MB-231 cells known to have a nuclear/perinuclear located PBR, PK11195, a specific PBR ligand enhanced the proliferation of cells, and the proliferative effect of PK11195 was reversed by an addition of lovastatin, a HMG-CoA reductase inhibitor. Diazepam- and flavonoids-induced cytotoxic activity in both cancer cell lines was not reduced by the addition of 5-fluorouracil (5-FU), a chemotherapeutic agent. Like flavonoids, diazepam inhibited the release of vascular endothelial growth factor (VEGF) and granulocyte-macrophage-colony stimulating factor (GM-CSF) into supernatants of cultured in the SNU-C4 and MDA-MB-231 cells. In conclusion, this study provided in vitro information on the safe use of sedative in oncologic patients.  (+info)

The synthetic triterpenoid CDDO-Im inhibits fatty acid synthase expression and has antiproliferative and proapoptotic effects in human liposarcoma cells. (4/23)

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A pathogenic fungi diphenyl ether phytotoxin targets plant enoyl (acyl carrier protein) reductase. (5/23)

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Increased fatty acid synthase as a potential therapeutic target in multiple myeloma. (6/23)

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Slow-onset inhibition of the FabI enoyl reductase from francisella tularensis: residence time and in vivo activity. (7/23)

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Surfactants, aromatic and isoprenoid compounds, and fatty acid biosynthesis inhibitors suppress Staphylococcus aureus production of toxic shock syndrome toxin 1. (8/23)

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