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Biochem Biophys Res Commun. 2014 Mar 7;445(2):346-51. doi: 10.1016/j.bbrc.2014.01.191. Epub 2014 Feb 6.

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.

Author information

1
Capital Medical University, 10 Xitoutiao, You An Men, Beijing 100069, PR China.
2
Capital Medical University, 10 Xitoutiao, You An Men, Beijing 100069, PR China. Electronic address: mingzhao@bjmu.edu.cn.
3
Capital Medical University, 10 Xitoutiao, You An Men, Beijing 100069, PR China. Electronic address: sqpeng@bjmu.edu.cn.

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.

KEYWORDS:

1,2,3,4,6-Penta-O-galloyl-β-d-glucose (PGG); Anti-tumour; Fatty acid synthase (FAS)

PMID:
24508804
DOI:
10.1016/j.bbrc.2014.01.191
[Indexed for MEDLINE]

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