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Rich66 · 04-15-2009, 11:30 AM

A later study which suggests it works, indicates mechanism and even a link to mTor:

1: J Biol Chem. 2008 Nov 14;283(46):31378-84. Epub 2008 Sep 16.Links: Inhibition of fatty-acid synthase induces caspase-8-mediated tumor cell apoptosis by up-regulating DDIT4.

Knowles LM, Yang C, Osterman A, Smith JW.
Cancer Research Center, Burham Institute for Medical Research, La Jolla, California 92037, USA.
Fatty-acid synthase (FAS) is up-regulated in a broad range of cancers, including those of the breast, prostate, and ovaries. In tumor cells, the inhibition of FAS elicits cell cycle arrest and apoptosis, so it is considered a potential drug target for oncology. Results from this study show that inhibition of FAS, by either knockdown with small interfering RNA or inhibition with the small molecule drug orlistat, leads to activation of the receptor-mediated apoptotic cascade (caspase-8-mediated) and ultimately to cell death. However, knockdown of two enzymes upstream of FAS, acetyl-CoA carboxylase-alpha and ATP-citrate lyase, fails to activate caspase-8 or to elicit apoptosis in tumor cells, even though palmitate synthesis was suppressed. Using differential gene analysis, we traced the unique apoptotic effect of FAS inhibition to up-regulation of DDIT4 (DNA damage-inducible transcript 4), a stress-response gene that negatively regulates the mTOR pathway. These findings indicate that suppression of palmitate synthesis is not sufficient for eliciting tumor cell death and suggest that the unique effect of inhibition of FAS results from negative regulation of the mTOR pathway via DDIT4.

04-15-2009, 11:30 AM	#2
Rich66 Senior Member Join Date: Feb 2008 Location: South East Wisconsin Posts: 3,431	A later study which suggests it works, indicates mechanism and even a link to mTor: 1: J Biol Chem. 2008 Nov 14;283(46):31378-84. Epub 2008 Sep 16.Links Inhibition of fatty-acid synthase induces caspase-8-mediated tumor cell apoptosis by up-regulating DDIT4. Knowles LM, Yang C, Osterman A, Smith JW. Cancer Research Center, Burham Institute for Medical Research, La Jolla, California 92037, USA. Fatty-acid synthase (FAS) is up-regulated in a broad range of cancers, including those of the breast, prostate, and ovaries. In tumor cells, the inhibition of FAS elicits cell cycle arrest and apoptosis, so it is considered a potential drug target for oncology. Results from this study show that inhibition of FAS, by either knockdown with small interfering RNA or inhibition with the small molecule drug orlistat, leads to activation of the receptor-mediated apoptotic cascade (caspase-8-mediated) and ultimately to cell death. However, knockdown of two enzymes upstream of FAS, acetyl-CoA carboxylase-alpha and ATP-citrate lyase, fails to activate caspase-8 or to elicit apoptosis in tumor cells, even though palmitate synthesis was suppressed. Using differential gene analysis, we traced the unique apoptotic effect of FAS inhibition to up-regulation of DDIT4 (DNA damage-inducible transcript 4), a stress-response gene that negatively regulates the mTOR pathway. These findings indicate that suppression of palmitate synthesis is not sufficient for eliciting tumor cell death and suggest that the unique effect of inhibition of FAS results from negative regulation of the mTOR pathway via DDIT4.