Novel and potent inhibitors of fatty acid synthase derived from catechins and their inhibition on MCF-7 cells.
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 microg/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.
Zhang
Shu-Yan
SY
College of Life Science, Graduate University of Chinese Academy of Sciences, Beijing, P.R. China.
Ma
Xiao-Feng
XF
Zheng
Chao-Gu
CG
Wang
Yan
Y
Cao
Xue-Li
XL
Tian
Wei-Xi
WX
D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002392:Catechin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D064429:Fatty Acid Synthases / Q000037:antagonists & inhibitors*; D005260:Female; D006801:Humans; D006851:Hydrochloric Acid / Q000737:chemistry; D020128:Inhibitory Concentration 50; D007700:Kinetics; D011422:Propionates / Q000737:chemistry; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013464:Sulfuric Acids / Q000737:chemistry
D004791:Enzyme Inhibitors; D011422:Propionates; D013464:Sulfuric Acids; D002392:Catechin; C045651:epigallocatechin gallate; D064429:Fatty Acid Synthases; C033158:sulfuric acid; D006851:Hydrochloric Acid