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Fatty acid synthase (FAS) is a multi-enzyme protein that catalyzes fatty acid synthesis. Its main function is to catalyze the synthesis of palmitate from acetyl-CoA and malonyl-CoA. FAS is a target for anticancer drug [1].

In human breast cancer cells, C 75 reacted preferentially with FAS and inhibited FAS. The antitumor activity of C 75 is likely mediated by its inhibition of FAS [1]. In primary cortical neurons, C 75 inhibited FAS activity and increased the activity of carnitine palmitoyltransferase-

1 (CPT-1) and fatty acid oxidation, which suggested that C 75 might influence cellular energy balance through regulation of these metabolic pathways. Also, C 75 altered neuronal ATP levels in a biphasic manner (decreasing initially, followed by a prolonged increase above control levels). The AMP-activated protein kinase (AMPK) activity was also influenced by C 75 [2]. In human melanoma A-375 cells, C 75 inhibited cell growth through activation of caspase-dependent apoptosis [3].

In diet induced obese (DIO) mice, chronic C 75 treatment reduced food intake and increased energy expenditure due to increased fatty acid oxidation. C 75 significantly reduced adipose tissue. The reduced food intake was accompanied by an increase in amphetamine and cocaine-related transcript expression [4].

References:

[1].  Kuhajda FP, Pizer ES, Li JN, et al. Synthesis and antitumor activity of an inhibitor of fatty acid synthase. Proc Natl Acad Sci U S A, 2000, 97(7): 3450-3454.

[2].  Landree LE, Hanlon AL, Strong DW, et al. C75, a fatty acid synthase inhibitor, modulates AMP-activated protein kinase to alter neuronal energy metabolism. J Biol Chem, 2004, 279(5): 3817-3827.

[3].  Ho TS, Ho YP, Wong WY, et al. Fatty acid synthase inhibitors cerulenin and C75 retard growth and induce caspase-dependent apoptosis in human melanoma A-375 cells. Biomed Pharmacother, 2007, 61(9): 578-587.

[4].  Thupari JN, Kim EK, Moran TH, et al. Chronic C75 treatment of diet-induced obese mice increases fat oxidation and reduces food intake to reduce adipose mass. Am J Physiol Endocrinol Metab, 2004, 287(1): E97-E104.

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