Deoxyverrucosidin, a novel GRP78/BiP down-regulator, produced by Penicillium sp.
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.
Choo
Soo-Jin
SJ
Laboratory of Antioxidants, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-333, Korea.
Park
Hae-Ryong
HR
Ryoo
In-Ja
IJ
Kim
Jong-Pyung
JP
Yun
Bong-Sik
BS
Kim
Chang-Jin
CJ
Shin-ya
Kazuo
K
Yoo
Ick-Dong
ID
D002460:Cell Line; D015536:Down-Regulation / Q000187:drug effects; D000091342:Endoplasmic Reticulum Chaperone BiP; D017930:Genes, Reporter; D006360:Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000187:drug effects*; D006801:Humans; D008156:Luciferases / Q000235:genetics; D009682:Magnetic Resonance Spectroscopy; D018832:Molecular Chaperones / Q000037:antagonists & inhibitors* / Q000187:drug effects*; D015394:Molecular Structure; D010407:Penicillium / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011753:Pyrones / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D021241:Spectrometry, Mass, Electrospray Ionization
D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D011753:Pyrones; C501242:deoxyverrucosidin; C048224:verrucosidin; D008156:Luciferases