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: Xing Fu Cai, Xuejun Jin, Dongho Lee, Young Taek Yang, Kyeong Lee, Young-Soo Hong, Jeong-Hyung Lee, Jung Joon Lee
• Journal: Journal of natural products (J Nat Prod) Vol. 69 Issue 7 Pg. 1095-7 (Jul 2006) ISSN: 0163-3864 [Print] United States
• PMID: 16872154 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• (15R)-hydroxycryptopleurine
• Alkaloids
• Hypoxia-Inducible Factor 1
• Vascular Endothelial Growth Factor A
• cryptopleurine

Topics

• Alkaloids (chemistry, isolation & purification, pharmacology)
• Boehmeria (chemistry)
• Dose-Response Relationship, Drug
• Humans
• Hypoxia (metabolism)
• Hypoxia-Inducible Factor 1 (antagonists & inhibitors)
• Inhibitory Concentration 50
• Korea
• Plant Roots (chemistry)
• Plants, Medicinal (chemistry)
• Stomach Neoplasms (metabolism)
• Vascular Endothelial Growth Factor A (antagonists & inhibitors)