Abstract
Glutathione transferase P1-1 is over expressed in some cancer cells and contributes to detoxification of anticancer drugs, leading to drug-resistant tumors. The inhibition of human recombinant GSTP1-1 by natural plant products was investigated using 10 compounds isolated from plants indigenous to Southern and Central Africa. Monochlorobimane and 1-chloro-2,4-dinitrobenzene were used to determine GST activity. Each test compound was screened at 33 and 100 µM. Isofuranonapthoquinone (1) (from Bulbine frutescens) showed 68% inhibition at 33 µM, and sesquiterpene lactone (2) (from Dicoma anomala) showed 75% inhibition at 33 μM. The IC(50) value of 1 was 6.8 μM. The mode of inhibition was mixed, partial (G site) and noncompetitive (H site) with K(i) values of 8.8 and 0.21 µM, respectively. Sesquiterpene 2 did not inhibit the CDNB reaction. Therefore, isofuranonapthoquinone 1 needs further investigations in vivo because of its potent inhibition of GSTP1-1 in vitro.
MeSH terms
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Biological Products / chemistry
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Biological Products / isolation & purification
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Biological Products / pharmacology*
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Cell Proliferation / drug effects
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Dose-Response Relationship, Drug
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Enzyme Activation / drug effects
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / isolation & purification
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Enzyme Inhibitors / pharmacology*
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Glutathione S-Transferase pi / antagonists & inhibitors*
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Glutathione S-Transferase pi / isolation & purification
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Glutathione S-Transferase pi / metabolism
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Humans
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Isoenzymes / antagonists & inhibitors*
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Isoenzymes / isolation & purification
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Isoenzymes / metabolism
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Kinetics
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Molecular Conformation
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Plant Extracts / chemistry
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Plant Extracts / isolation & purification
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Plant Extracts / pharmacology
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Recombinant Proteins / antagonists & inhibitors
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Recombinant Proteins / isolation & purification
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Recombinant Proteins / metabolism
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Stereoisomerism
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Structure-Activity Relationship
Substances
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Biological Products
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Enzyme Inhibitors
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Isoenzymes
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Plant Extracts
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Recombinant Proteins
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GSTP1 protein, human
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Glutathione S-Transferase pi