Fatty acid synthase is a potential molecular target for the chemoprevention of breast cancer.
The purpose of this investigation was to determine whether fatty acid synthase (FAS) is a potential molecular target for the chemoprevention of breast cancer by evaluating the effect of the FAS inhibitor triclosan on rat mammary carcinogenesis. At 50 days of age, 60 female Sprague-Dawley rats received 50 mg/kg methylnitrosourea (MNU) i.p. to initiate mammary carcinogenesis. One week later, half of the rats were fed triclosan at a level of 1000 p.p.m. in an AIN-93G diet for the remainder of the experiment. The other 30 control rats were fed an AIN-93G diet without triclosan. Twelve weeks after MNU treatment, 70% of control rats had mammary adenocarcinomas compared with only 43.3% of the triclosan group (P < 0.05). The control rats had an average of 2.7 +/- 0.3 tumors/rat compared with 1.8 +/- 0.3 in the triclosan group (P < 0.05). Western analysis showed that the tumors in the control rats expressed high levels of FAS. Immunohistochemistry showed that sections of tumors that stained strongly for FAS also showed strong staining for proliferating cell nuclear antigen. Furthermore, at biologically relevant dose levels, triclosan inhibited the activity of FAS in mammary tumor homogenates. These results indicate that triclosan suppresses rat mammary carcinogenesis by inhibiting FAS and suggest that FAS is a promising molecular target for breast cancer chemoprevention.
Lu
Suying
S
Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Ontario, M5S 3E2, Canada.
Archer
Michael C
MC
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D015153:Blotting, Western; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D064429:Fatty Acid Synthases / Q000187:drug effects* / Q000378:metabolism*; D005260:Female; D007150:Immunohistochemistry; D008325:Mammary Neoplasms, Experimental / Q000517:prevention & control*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014260:Triclosan / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D018809:Proliferating Cell Nuclear Antigen; D014260:Triclosan; D064429:Fatty Acid Synthases