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The fatty acid synthase inhibitor triclosan: repurposing an anti-microbial agent for targeting prostate cancer

Overview of attention for article published in Oncotarget, September 2014
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Title
The fatty acid synthase inhibitor triclosan: repurposing an anti-microbial agent for targeting prostate cancer
Published in
Oncotarget, September 2014
DOI 10.18632/oncotarget.2433
Pubmed ID
Authors

Martin C. Sadowski, Rebecca H. Pouwer, Jennifer H. Gunter, Amy A. Lubik, Ronald J. Quinn, Colleen C. Nelson

Abstract

Inhibition of FASN has emerged as a promising therapeutic target in cancer, and numerous inhibitors have been investigated. However, severe pharmacological limitations have challenged their clinical testing. The synthetic FASN inhibitor triclosan, which was initially developed as a topical antibacterial agent, is merely affected by these pharmacological limitations. Yet, little is known about its mechanism in inhibiting the growth of cancer cells. Here we compared the cellular and molecular effects of triclosan in a panel of eight malignant and non-malignant prostate cell lines to the well-known FASN inhibitors C75 and orlistat, which target different partial catalytic activities of FASN. Triclosan displayed a superior cytotoxic profile with a several-fold lower IC50 than C75 or orlistat. Structure-function analysis revealed that alcohol functionality of the parent phenol is critical for inhibitory action. Rescue experiments confirmed that end product starvation was a major cause of cytotoxicity. Importantly, triclosan, C75 and orlistat induced distinct changes to morphology, cell cycle, lipid content and the expression of key enzymes of lipid metabolism, demonstrating that inhibition of different partial catalytic activities of FASN activates different metabolic pathways. These finding combined with its well-documented pharmacological safety profile make triclosan a promising drug candidate for the treatment of prostate cancer.

Mendeley readers

The data shown below were compiled from readership statistics for 88 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 1 1%
France 1 1%
Unknown 86 98%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 18 20%
Other 15 17%
Researcher 13 15%
Student > Bachelor 8 9%
Student > Doctoral Student 6 7%
Other 17 19%
Unknown 11 13%
Readers by discipline Count As %
Agricultural and Biological Sciences 25 28%
Medicine and Dentistry 14 16%
Biochemistry, Genetics and Molecular Biology 9 10%
Chemistry 8 9%
Pharmacology, Toxicology and Pharmaceutical Science 3 3%
Other 11 13%
Unknown 18 20%