Journal
BIOMEDICINE & PHARMACOTHERAPY
Volume 65, Issue 4, Pages 286-292Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2011.02.016
Keywords
Fatty acid synthase; Human colorectal carcinoma; Orlistat
Funding
- National Science Council, Taipei, Taiwan [NSC97-2314-B-010-046-MY3]
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We established a HT-29/tk-luc human colorectal carcinoma-bearing animal model for the study of the inhibition effect and mechanism of orlistat, a fatty acid synthase (FASN) inhibitor. The results showed that orlistat caused cell cycle arrest at G1 phase, and triggered apoptosis through caspase-3 activation. The tumor inhibition effect of orlistat may also due to the inhibition of fatty acid synthesis without altering FASN activity. The tumor size of orlistat-treated mice in vivo was significantly smaller than that of the controls with 55% inhibition. The therapeutic efficacy was further confirmed with the bioluminescent imaging and nuclear molecular imaging with (131)I-FIAU/gamma scintigraphy and (11)C-acetate/microPET. We suggest that FASN is a potential target for the treatment of human colorectal carcinoma. (C) 2011 Elsevier Masson SAS. All rights reserved.
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