Phenanthroquinolizidine alkaloids from the roots of Boehmeria pannosa potently inhibit hypoxia-inducible factor-1 in AGS human gastric cancer cells

J Nat Prod. 2006 Jul;69(7):1095-7. doi: 10.1021/np060081y.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / chemistry
  • Alkaloids / isolation & purification*
  • Alkaloids / 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

Substances

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