Terpenoid tetrahydroisoquinoline alkaloids emetine, klugine, and isocephaeline inhibit the activation of hypoxia-inducible factor-1 in breast tumor cells

J Nat Prod. 2005 Jun;68(6):947-50. doi: 10.1021/np050029m.

Abstract

Klugine (1), isocephaeline (2), and emetine (4) inhibited hypoxia-inducible factor-1 (HIF-1) activation by hypoxia in T47D breast tumor cells (IC(50) values 0.2, 1.1, and 0.11 muM, respectively). Compounds 1, 2, and 4 inhibited both hypoxia- and iron chelator-induced HIF-1 activation by blocking HIF-1alpha protein accumulation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alkaloids / chemistry*
  • Alkaloids / pharmacology*
  • Breast Neoplasms
  • DNA-Binding Proteins / drug effects*
  • Emetine / chemistry*
  • Emetine / pharmacology*
  • Humans
  • Hypoxia-Inducible Factor 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Molecular Structure
  • Nuclear Proteins / drug effects*
  • Quinazolines / chemistry*
  • Quinazolines / pharmacology*
  • Rubiaceae / chemistry
  • Terpenes / chemistry*
  • Terpenes / pharmacology*
  • Tetrahydroisoquinolines / chemistry*
  • Tetrahydroisoquinolines / pharmacology*
  • Transcription Factors / drug effects*
  • Tumor Cells, Cultured
  • Vascular Endothelial Growth Factor A / analysis

Substances

  • Alkaloids
  • DNA-Binding Proteins
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Nuclear Proteins
  • Quinazolines
  • Terpenes
  • Tetrahydroisoquinolines
  • Transcription Factors
  • Vascular Endothelial Growth Factor A
  • isocephaeline
  • klugine
  • Emetine