Abstract
Glucose-regulated protein 78 (GRP78) resides in endoplasmic reticulum (ER) and plays a role in protecting tumor cells against the toxic effects of anticancer agents. During the search for down-regulators of GRP78 using a reporter gene (luciferase) assay system, we isolated a novel compound designated as deoxyverrucosidin (1), a congener of verrucosidin (2), from Penicillium sp. and identified it as a down-regulator of the grp78 gene. The structure of 1 was determined by mainly ESI-mass and two-dimensional NMR spectra. 1 dose-dependently inhibited the expression of GRP78 promoter with an IC50 of 30 nM.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Cell Line
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Down-Regulation / drug effects
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Endoplasmic Reticulum Chaperone BiP
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Genes, Reporter
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Heat-Shock Proteins / antagonists & inhibitors*
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Heat-Shock Proteins / drug effects*
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Humans
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Luciferases / genetics
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Magnetic Resonance Spectroscopy
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Molecular Chaperones / antagonists & inhibitors*
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Molecular Chaperones / drug effects*
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Molecular Structure
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Penicillium / metabolism*
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Promoter Regions, Genetic / drug effects
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Pyrones / chemistry*
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Pyrones / metabolism
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Pyrones / pharmacology*
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Spectrometry, Mass, Electrospray Ionization
Substances
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Endoplasmic Reticulum Chaperone BiP
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HSPA5 protein, human
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Heat-Shock Proteins
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Molecular Chaperones
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Pyrones
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deoxyverrucosidin
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verrucosidin
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Luciferases