Deoxyverrucosidin, a novel GRP78/BiP down-regulator, produced by Penicillium sp.

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.

• Authors: Soo-Jin Choo, Hae-Ryong Park, In-Ja Ryoo, Jong-Pyung Kim, Bong-Sik Yun, Chang-Jin Kim, Kazuo Shin-ya, Ick-Dong Yoo
• Journal: The Journal of antibiotics (J Antibiot (Tokyo)) Vol. 58 Issue 3 Pg. 210-3 (Mar 2005) ISSN: 0021-8820 [Print] England
• PMID: 15895531 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Endoplasmic Reticulum Chaperone BiP
• HSPA5 protein, human
• Heat-Shock Proteins
• Molecular Chaperones
• Pyrones
• deoxyverrucosidin
• verrucosidin
• Luciferases

Topics

• Cell Line
• Down-Regulation (drug effects)
• Endoplasmic Reticulum Chaperone BiP
• Genes, Reporter
• Heat-Shock Proteins (antagonists & inhibitors, drug effects)
• Humans
• Luciferases (genetics)
• Magnetic Resonance Spectroscopy
• Molecular Chaperones (antagonists & inhibitors, drug effects)
• Molecular Structure
• Penicillium (metabolism)
• Promoter Regions, Genetic (drug effects)
• Pyrones (chemistry, metabolism, pharmacology)
• Spectrometry, Mass, Electrospray Ionization