title: Phenanthroquinolizidine alkaloids from the roots of Boehmeria pannosa potently inhibit hypoxia-inducible factor-1 in AGS human gastric cancer cells.
abstract: A bioassay-guided phytochemical investigation on the methanol extract of Boehmeria pannosa, using a HIF-1-mediated reporter gene assay, led to the isolation of two phenanthroquinolizidine alkaloids, (-)-cryptopleurine (1) and (-)-(15R)-hydroxycryptopleurine (2). The structure of the new compound 2 was determined by spectroscopic methods. Compounds 1 and 2 potently inhibited the hypoxia-induced expression of a reporter gene under the control of a hypoxia response element (HRE) with IC(50) values of 8.7 and 48.1 nM, respectively. Furthermore, 1 and 2 suppressed the accumulation of HIF-1alpha protein in a dose-dependent manner, but not the HIF-1beta protein and inhibited expression of vascular endothelial growth factor (VEGF) by hypoxia.
authors.affiliation: Korea Research Institute of Bioscience and Biotechnology, P.O. Box 115, Yuseong, Daejeon 305-600, Korea.
authors.forename: Xing Fu
authors.initials: XF
authors.lastname: Cai
authors.forename: Xuejun
authors.initials: X
authors.lastname: Jin
authors.forename: Dongho
authors.initials: D
authors.lastname: Lee
authors.forename: Young Taek
authors.initials: YT
authors.lastname: Yang
authors.forename: Kyeong
authors.initials: K
authors.lastname: Lee
authors.forename: Young-Soo
authors.initials: YS
authors.lastname: Hong
authors.forename: Jeong-Hyung
authors.initials: JH
authors.lastname: Lee
authors.forename: Jung Joon
authors.initials: JJ
authors.lastname: Lee
mesh_terms: D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D032402:Boehmeria / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D051793:Hypoxia-Inducible Factor 1 / Q000037:antagonists & inhibitors*; D020128:Inhibitory Concentration 50; D007723:Korea; D018517:Plant Roots / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry*; D013274:Stomach Neoplasms / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
chemical_list: C513465:(15R)-hydroxycryptopleurine; D000470:Alkaloids; D051793:Hypoxia-Inducible Factor 1; D042461:Vascular Endothelial Growth Factor A; C007160:cryptopleurine