Description
TOFA (54857-86-2) interferes with fatty acid synthase via inhibition of acetyl Co-A carboxylase (ACC1).1 Induces apoptosis in a variety of tumor cell lines.2,3 Stimulates neurite outgrowth and neuronal differentiation in rat pheochromocytoma cells.4 TOFA impairs glucose-stimulated insulin secretion after chronic treatment.5
Uses
TOFA has been used as a lipid biosynthesis inhibitor in mesenchymal stromal cells (MSCs), human pluripotent stem cells., an acetyl-CoA carboxylase 1 inhibitor in murine adipocyte cell lines., a lipolysis inhibitor in cancer stem cells (CSCs).
Definition
ChEBI: A member of the class of furans that is 2-furoic acid in which the hydrogen at position 5 is replaced by a tetradecyloxy group.
Biochem/physiol Actions
5-(Tetradecyloxy)-2-furoic acid (TOFA) elicits hypolipidemic?functionality by favoring fatty acid breakdown and at the same time preventing biosynthesis. It induces apoptosis in pancreatic cancer cells and favors tumor suppression.
in vivo
TOFA inhibits COC1/DDP cell growth in ovarian tumor mouse xenografts. The tumor growth rate is signifi cantly inhibited by TOFA compared with the DMSO treated control mice (1649±356.3 vs. 5128±390.4 mm3. No toxicity is observed in the heart, liver, spleen, lung, kidney and intestinal tissues. By inhibiting ACC, TOFA may be a promising small molecule agent for ovarian cancer therapy[2].
References
References/Citations:
1) Halvorson?et al. (1984),?Inhibition of fatty acid synthesis in isolated adipocytes by 5-tetradecyloxy)-2-furoic acid; Lipids,?19?851
2) Guseva?et al. (2011),?TOFA (5-tetradecyl-oxy-2-furoic acid) reduces fatty acid synthesis, inhibits expression of AR, neuropilin-1 and Mcl-1 and kills prostate cancer cells independent of p53 status; Cancer Biol. Ther.,?12?80
3) Zhou?et al. (2003),?Fatty acid synthesis inhibition triggers apoptosis during S phase in human cancer cells; Cancer Res.,?63?7330
4) Schmidt?et al. (1999),?Transcription control and neuronal differentiation by agents that activate the LXR nuclear receptor family; Mol. Cell. Endocrinol.,?155?51
5) Ronnebaum?et al. (2008),?Chronic suppression of acetyl-CoA carboxylase 1 in beta-cells impairs insulin secretion via inhibition of glucose rather than lipid metabolism; J. Biol. Chem.,?283?14248
