title: In vitro inhibition of fatty acid synthase by 1,2,3,4,6-penta-O-galloyl-β-D-glucose plays a vital role in anti-tumour activity.
abstract: 1,2,3,4,6-Penta-O-galloyl-β-D-glucose (PGG) inhibits glioma cancer U251 cells, more strongly than MDA-MB-231 and U87 cells. In addition, PGG is transported across cancer cell membrane to further down-regulate FAS and activate caspase-3 in MDA-MB-231 cells. Compared with other FAS inhibitors, including catechin gallate and morin, PGG involves a higher reversible fast-binding inhibition with half-inhibitory concentration value (IC50) of 1.16 μM and an irreversible slow-binding inhibition, i.e. saturation kinetics with a dissociation constant of 0.59 μM and a limiting rate constant of 0.16 min(-l). The major reacting site of PGG is on the β-ketoacyl reduction domain of FAS. PGG exhibits different types of inhibitions against the three substrates in the FAS overall reaction. The higher concentrations of PGG tested (higher than 20 μM) clearly altered the secondary structure of FAS by increasing the α-helix and induced a redshift in the FAS spectra. In addition, only PGG concentrations higher than 20 μM resulted in FAS precipitation.
authors: Capital Medical University, 10 Xitoutiao, You An Men, Beijing 100069, PR China.
authors: Wenhua
authors: W
authors: Zhao
authors: Capital Medical University, 10 Xitoutiao, You An Men, Beijing 100069, PR China.
authors: Yuji
authors: Y
authors: Wang
authors: Capital Medical University, 10 Xitoutiao, You An Men, Beijing 100069, PR China.
authors: Weijia
authors: W
authors: Hao
authors: Capital Medical University, 10 Xitoutiao, You An Men, Beijing 100069, PR China. Electronic address: mingzhao@bjmu.edu.cn.
authors: Ming
authors: M
authors: Zhao
authors: Capital Medical University, 10 Xitoutiao, You An Men, Beijing 100069, PR China. Electronic address: sqpeng@bjmu.edu.cn.
authors: Shiqi
authors: S
authors: Peng
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D064429:Fatty Acid Synthases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D047348:Hydrolyzable Tannins / Q000494:pharmacology*; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D047348:Hydrolyzable Tannins; C435084:pentagalloylglucose; D064429:Fatty Acid Synthases
keywords: 1,2,3,4,6-Penta-O-galloyl-β-d-glucose (PGG); Anti-tumour; Fatty acid synthase (FAS)