Novel and potent inhibitors of fatty acid synthase derived from catechins and their inhibition on MCF-7 cells

Abstract

Fatty acid synthase (FAS) is a potential target for cancer, but potent inhibitors against FAS are scarce. In this study, we found that activities of catechins on inhibiting FAS increased greatly by heating them in acid. The enhancement was positively correlated to H⁺ concentration. The inhibitory activities of the final products from different catechins were similar, all of which were less than 1 μg/mL. The product from ( − )-epigallocatechin gallate (EGCG) was stable at room temperature, and its inhibitory kinetics and reacting sites on FAS were obviously different from the known FAS inhibitors. It also affected the viability of MCF-7 cells more obviously than EGCG. A putative route of the reaction progress was proposed and the effective inhibitors were deduced to be oligomers of 2-hydroxy-3-(3′, 4′, 5′-trihydroxyphenyl) propenoic acid by analysis of their spectra. The work affords new and potent FAS inhibitors that would be promising candidates for the treatment of cancer.

Keywords::

• Fatty acid synthase
• inhibitor
• catechins
• oligomers
• anticancer activity

Acknowledgements

This work was supported by Grants 30572252 and 30670455 of the National Natural Science Foundation of China. We appreciate the help of Dr. Yang Jing-Kui (Chemistry College of GUCAS, Beijing, China) on the analysis of the chemical reaction and molecular structure.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.