Phenanthroquinolizidine alkaloids from the roots of Boehmeria pannosa potently inhibit hypoxia-inducible factor-1 in AGS human gastric cancer cells.
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.
Cai
Xing Fu
XF
Korea Research Institute of Bioscience and Biotechnology, P.O. Box 115, Yuseong, Daejeon 305-600, Korea.
Jin
Xuejun
X
Lee
Dongho
D
Yang
Young Taek
YT
Lee
Kyeong
K
Hong
Young-Soo
YS
Lee
Jeong-Hyung
JH
Lee
Jung Joon
JJ
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
C513465:(15R)-hydroxycryptopleurine; D000470:Alkaloids; D051793:Hypoxia-Inducible Factor 1; D042461:Vascular Endothelial Growth Factor A; C007160:cryptopleurine