Evaluation of the inhibitory activities of aceraceous plants on fatty acid synthase.
Fatty acid synthase (FAS) is a very significant lipogenic enzyme participating in energy metabolism in vivo and has been reported as a potential new therapeutic target for cancer treatment. The extracts from sixteen Aceraceae were prepared to assay their inhibitory activities against duck liver FAS and their correlated antitumor bioactivity. Their inhibition of FAS was composed of a reversible fast-binding inhibition, by which 0.41 microg/mL of the A. campestre extract inhibits 50% FAS activity, and an irreversible slow-binding inhibition with inactivation rate constants, k(obs), ranging between 1.5 x 10(-3) and 10.6 x 10(-3) min(-1). Three Aceraceae extracts were selected from their smaller IC50 values to study different type of inhibitions against the three substrates in the FAS overall reaction. As compared with other reported FAS inhibitors including EGCG with regard to inhibition constant and IC50 value, the extracts appeared to be more efficient inhibitors, and exhibited a considerable inhibition against the growth of five types of cancer cells (China patent application number 200610088901.6), which may be related to the inhibition of lipogenesis in these cells.
Zhao
Wen-Hua
WH
Department of Chemical Biology, School of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, China.
Gao
ChunChun
C
Zhang
Ying-Xia
YX
Tian
Wei-Xi
WX
D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D064429:Fatty Acid Synthases / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D005419:Flavonoids / Q000737:chemistry; D006801:Humans; D020128:Inhibitory Concentration 50; D007700:Kinetics; D010936:Plant Extracts / Q000494:pharmacology; D010940:Plant Proteins / Q000737:chemistry; D013056:Spectrophotometry, Ultraviolet; D013997:Time Factors
D004791:Enzyme Inhibitors; D005419:Flavonoids; D010936:Plant Extracts; D010940:Plant Proteins; D064429:Fatty Acid Synthases