Terpenoid tetrahydroisoquinoline alkaloids emetine, klugine, and isocephaeline inhibit the activation of hypoxia-inducible factor-1 in breast tumor cells.
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.
National Center for Natural Products Research and Department of Pharmacognosy, Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, University, 38677, USA.
Yu-Dong
YD
Zhou
Yong-Pil
YP
Kim
Kaleem Asjad
KA
Mohammed
Deborah K
DK
Jones
Ilias
I
Muhammad
D Chuck
DC
Dunbar
Dale G
DG
Nagle
D000470:Alkaloids / Q000737:chemistry* / Q000494:pharmacology*; D001943:Breast Neoplasms; D004268:DNA-Binding Proteins / Q000187:drug effects*; D004640:Emetine / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D015394:Molecular Structure; D009687:Nuclear Proteins / Q000187:drug effects*; D011799:Quinazolines / Q000737:chemistry* / Q000494:pharmacology*; D019666:Rubiaceae / Q000737:chemistry; D013729:Terpenes / Q000737:chemistry* / Q000494:pharmacology*; D044005:Tetrahydroisoquinolines / Q000737:chemistry* / Q000494:pharmacology*; D014157:Transcription Factors / Q000187:drug effects*; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis
D000470:Alkaloids; D004268:DNA-Binding Proteins; C497442:HIF1A protein, human; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins; D011799:Quinazolines; D013729:Terpenes; D044005:Tetrahydroisoquinolines; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; C502716:isocephaeline; C480052:klugine; D004640:Emetine